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51.428571 0 2744.77 Tm 6.358333 0 Td 50.231481 Tz (Patent ) Tj 1.944444 0 Td 52.146465 Tz (Application ) Tj 3.616667 0 Td 59.41358 Tz (No. ) Tj 1.283333 0 Td 52.146465 Tz (61/254,981, ) Tj 3.636111 0 Td 43.425926 Tz (filed ) Tj 1.477778 0 Td 61.574074 Tz (on ) Tj 0.913889 0 Td 51.041667 Tz (Oct. ) Tj 1.4 0 Td 50.771605 Tz (26, ) Tj 1.088889 0 Td 53.796296 Tz (2009. ) Tj 38.571429 0 0 38.571429 0 2672 Tm 14.181481 0 Td 90.740741 Tz (FIELD ) Tj 2.981481 0 Td 101.54321 Tz (OF ) Tj 1.451852 0 Td 105.144033 Tz (THE ) Tj 2.177778 0 Td 98.422497 Tz (INVENTION ) Tj 51.428571 0 0 51.428571 0 2584.016393 Tm 7.097222 0 Td 57.685185 Tz (Novel ) Tj 1.944444 0 Td 59.41358 Tz (and ) Tj 1.263889 0 Td 54.012346 Tz (optimized ) Tj 3.091667 0 Td 48.148148 Tz (classes ) Tj 2.216667 0 Td 58.333333 Tz (of ) Tj 0.836111 0 Td 53.652263 Tz (pipemidic ) Tj 3.091667 0 Td 51.041667 Tz (acid ) Tj 1.438889 0 Td 47.638889 Tz (derivative ) Tj 51.428571 0 0 51.428571 0 2543.750636 Tm 6.358333 0 Td 61.934156 Tz (compounds ) Tj 3.752778 0 Td 46.180556 Tz (that ) Tj 1.458333 0 Td 48.611111 Tz (exhibit ) Tj 2.430556 0 Td 46.450617 Tz (effective ) Tj 2.897222 0 Td 46.990741 Tz (inhibition ) Tj 3.208333 0 Td 59.953704 Tz (of ) Tj 1.011111 0 Td 50.771605 Tz (autotaxin ) Tj 51.428571 0 0 51.428571 0 2508.377171 Tm 6.358333 0 Td 60.185185 Tz (enzymes ) Tj 2.780556 0 Td 51.851852 Tz (are ) Tj 1.186111 0 Td 50.411523 Tz (provided. ) Tj 3.013889 0 Td 59.953704 Tz (Such ) Tj 1.730556 0 Td 47.222222 Tz (classes ) Tj 2.255556 0 Td 58.333333 Tz (of ) Tj 0.894444 0 Td 61.574074 Tz (compounds ) Tj 3.577778 0 Td 48.611111 Tz (exhibit ) Tj 51.428571 0 0 51.428571 0 2468.874845 Tm 6.358333 0 Td 45.37037 Tz (reactivity ) Tj 2.936111 0 Td 52.662037 Tz (with ) Tj 1.458333 0 Td 50.411523 Tz (autotaxin ) Tj 2.955556 0 Td 43.75 Tz (to ) Tj 0.758333 0 Td 48.611111 Tz (ultimately ) Tj 3.169444 0 Td 52.932099 Tz (reduce ) Tj 2.080556 0 Td 49.691358 Tz (the ) Tj 1.108333 0 Td 46.180556 Tz (size ) Tj 1.283333 0 Td 61.574074 Tz (of ) Tj 0.836111 0 Td 49.691358 Tz (the ) Tj 51.428571 0 0 51.428571 0 2431.113208 Tm 6.358333 0 Td 47.395833 Tz (reactive ) Tj 2.430556 0 Td 42.12963 Tz (sites ) Tj 1.4 0 Td 51.851852 Tz (thereon ) Tj 2.333333 0 Td 45.37037 Tz (to ) Tj 0.7 0 Td 51.388889 Tz (prevent ) Tj 2.294444 0 Td 52.175926 Tz (conversion ) Tj 3.286111 0 Td 56.712963 Tz (of ) Tj 0.758333 0 Td 54.594017 Tz (lysophosphati ) Tj 51.428571 0 0 51.428571 0 2392.857482 Tm 6.358333 0 Td 54.12037 Tz (dylcholine ) Tj 3.383333 0 Td 46.990741 Tz (to ) Tj 0.738889 0 Td 51.635802 Tz (lysophophatidic ) Tj 4.822222 0 Td 45.37037 Tz (acid. ) Tj 1.594444 0 Td 52.121914 Tz (Furthermore, ) Tj 3.947222 0 Td 54.282407 Tz (such ) Tj 1.477778 0 Td 83.179012 Tz (com ) Tj 51.428571 0 0 51.428571 0 2354.980861 Tm 6.358333 0 Td 58.333333 Tz (pounds ) Tj 2.255556 0 Td 55.092593 Tz (can ) Tj 1.147222 0 Td 59.953704 Tz (be ) Tj 0.894444 0 Td 50.771605 Tz (incorporated ) Tj 3.830556 0 Td 50.771605 Tz (within ) Tj 2.002778 0 Td 48.611111 Tz (delivery ) Tj 2.488889 0 Td 57.037037 Tz (forms ) Tj 1.866667 0 Td 48.611111 Tz (for ) Tj 0.972222 0 Td 68.055556 Tz (human ) Tj 51.428571 0 0 51.428571 0 2316.232737 Tm 6.358333 0 Td 46.990741 Tz (ingestion. ) Tj 3.130556 0 Td 66.435185 Tz (As ) Tj 1.147222 0 Td 49.907407 Tz (such, ) Tj 1.808333 0 Td 50.555556 Tz (these ) Tj 1.847222 0 Td 61.574074 Tz (compounds ) Tj 3.655556 0 Td 53.472222 Tz (accord ) Tj 2.236111 0 Td 58.333333 Tz (an ) Tj 1.030556 0 Td 48.611111 Tz (excellent ) Tj 51.428571 0 0 51.428571 0 2279.245863 Tm 6.358333 0 Td 62.114198 Tz (manner ) Tj 2.372222 0 Td 56.712963 Tz (of ) Tj 0.738889 0 Td 47.138047 Tz (potentially ) Tj 3.305556 0 Td 53.06713 Tz (reducing ) Tj 2.683333 0 Td 51.203704 Tz (generation ) Tj 3.286111 0 Td 56.712963 Tz (of ) Tj 0.758333 0 Td 46.759259 Tz (certain ) Tj 2.158333 0 Td 51.388889 Tz (cancers ) Tj 51.428571 0 0 51.428571 0 2239.92233 Tm 6.358333 0 Td 45.910494 Tz (attributable ) Tj 3.519444 0 Td 45.37037 Tz (to ) Tj 0.777778 0 Td 49.691358 Tz (the ) Tj 1.088889 0 Td 53.06713 Tz (presence ) Tj 2.780556 0 Td 56.712963 Tz (of ) Tj 0.836111 0 Td 46.8107 Tz (naturally ) Tj 2.761111 0 Td 51.49177 Tz (occurring ) Tj 2.994444 0 Td 50.771605 Tz (autotaxin ) Tj 51.428571 0 0 51.428571 0 2200.439376 Tm 6.338889 0 Td 51.851852 Tz (within ) Tj 2.041667 0 Td 50.771605 Tz (the ) Tj 1.05 0 Td 66.111111 Tz (human ) Tj 2.158333 0 Td 51.851852 Tz (body. ) Tj 1.769444 0 Td 59.722222 Tz (Methods ) Tj 2.683333 0 Td 58.333333 Tz (of ) Tj 0.797222 0 Td 46.990741 Tz (inactivating ) Tj 3.519444 0 Td 50.411523 Tz (autotaxin ) Tj 2.897222 0 Td 46.990741 Tz (to ) Tj 51.428571 0 0 51.428571 0 2164.619048 Tm 6.358333 0 Td 46.759259 Tz (certain ) Tj 2.177778 0 Td 51.851852 Tz (degrees ) Tj 2.372222 0 Td 50.411523 Tz (therewith ) Tj 2.936111 0 Td 54.282407 Tz (Such ) Tj 1.516667 0 Td 61.574074 Tz (compounds ) Tj 3.5 0 Td 50.771605 Tz (are ) Tj 1.069444 0 Td 59.511785 Tz (encompassed ) Tj 40 0 0 40 0 2130 Tm 8.15 0 Td 66.666667 Tz (within ) Tj 2.675 0 Td 63.888889 Tz (invention ) Tj 3.675 0 Td 64.583333 Tz (as ) Tj 1.025 0 Td 60.833333 Tz (well. ) Tj 38.571429 0 0 38.571429 0 2054 Tm 12.366667 0 Td 112.345679 Tz (BACKGROUND ) Tj 6.974074 0 Td 101.54321 Tz (OF ) Tj 1.451852 0 Td 106.584362 Tz (THE ) Tj 2.177778 0 Td 94.197531 Tz (PRIOR ) Tj 3.033333 0 Td 103.703704 Tz (ART ) Tj 48.571429 0 0 48.571429 0 1965 Tm 7.514706 0 Td 54.215686 Tz (Autotaxin, ) Tj 3.438235 0 Td 50.612745 Tz (also ) Tj 1.4 0 Td 68.627451 Tz (known ) Tj 2.244118 0 Td 53.186275 Tz (as ) Tj 0.782353 0 Td 69.485294 Tz (ATX, ) Tj 1.873529 0 Td 74.117647 Tz (ENPP2 ) Tj 2.408824 0 Td 54.901961 Tz (or ) Tj 0.782353 0 Td 66.568627 Tz (NPP2, ) Tj 2.202941 0 Td 50.784314 Tz (short ) Tj 1.688235 0 Td 51.470588 Tz (for ) Tj 51.428571 0 0 51.428571 0 1930.02503 Tm 6.377778 0 Td 51.851852 Tz (Ectonucleotide ) Tj 4.569444 0 Td 54.444444 Tz (pyrophosphatase ) Tj 5.113889 0 Td 52.423747 Tz (phosphodiesterase ) Tj 5.6 0 Td 43.75 Tz (2, ) Tj 0.777778 0 Td 37.268519 Tz (is ) Tj 0.680556 0 Td 61.574074 Tz (an ) Tj 51.428571 0 0 51.428571 0 1887.9388 Tm 6.358333 0 Td 63.194444 Tz (enzyme ) Tj 2.469444 0 Td 49.826389 Tz (secreted ) Tj 2.566667 0 Td 51.311728 Tz (within ) Tj 2.061111 0 Td 49.691358 Tz (the ) Tj 1.069444 0 Td 66.111111 Tz (human ) Tj 2.197222 0 Td 52.5 Tz (body. ) Tj 1.75 0 Td 54.282407 Tz (This ) Tj 1.555556 0 Td 55.092593 Tz (molecule ) Tj 2.819444 0 Td 54.012346 Tz (has ) Tj 51.428571 0 0 51.428571 0 1851.265497 Tm 6.338889 0 Td 58.333333 Tz (been ) Tj 1.497222 0 Td 65.462963 Tz (known ) Tj 2.1 0 Td 48.611111 Tz (for ) Tj 0.952778 0 Td 51.527778 Tz (generating ) Tj 3.208333 0 Td 59.62963 Tz (\(LPA\) ) Tj 1.886111 0 Td 53.703704 Tz (through ) Tj 2.391667 0 Td 52.824074 Tz (conversion ) Tj 3.286111 0 Td 53.472222 Tz (of ) Tj 0.719444 0 Td 59.953704 Tz (lyso ) Tj 51.428571 0 0 51.428571 0 1815.53271 Tm 6.358333 0 Td 51.203704 Tz (phosphatidyl-choline ) Tj 6.280556 0 Td 60.925926 Tz (\(LPC\) ) Tj 1.983333 0 Td 47.222222 Tz (thereto ) Tj 2.177778 0 Td 46.450617 Tz (via ) Tj 1.011111 0 Td 52.614379 Tz (lysophospholipase ) Tj 5.522222 0 Td 81.018519 Tz (D ) Tj 51.428571 0 0 51.428571 0 1774.782609 Tm 6.358333 0 Td 44.965278 Tz (activity ) Tj 2.469444 0 Td 46.990741 Tz (\(the ) Tj 1.438889 0 Td 55.555556 Tz (removal ) Tj 2.644444 0 Td 59.953704 Tz (of ) Tj 0.913889 0 Td 50.925926 Tz (choline ) Tj 2.430556 0 Td 58.333333 Tz (from ) Tj 1.730556 0 Td 48.611111 Tz (the ) Tj 1.147222 0 Td 55.092593 Tz (base ) Tj 1.594444 0 Td 65.219907 Tz (compound ) Tj 51.428571 0 0 51.428571 0 1734.362319 Tm 6.358333 0 Td 50.771605 Tz (generates ) Tj 2.916667 0 Td 55.740741 Tz (LPA\). ) Tj 1.866667 0 Td 71.296296 Tz (LPA ) Tj 1.419444 0 Td 52.932099 Tz (has ) Tj 1.108333 0 Td 57.523148 Tz (been ) Tj 1.516667 0 Td 47.800926 Tz (realized ) Tj 2.45 0 Td 45.37037 Tz (to ) Tj 0.680556 0 Td 48.935185 Tz (contribute ) Tj 3.072222 0 Td 45.37037 Tz (to ) Tj 0.719444 0 Td 58.333333 Tz (tumor ) Tj 51.428571 0 0 51.428571 0 1699.400955 Tm 6.358333 0 Td 43.75 Tz (cell ) Tj 1.205556 0 Td 52.777778 Tz (growth, ) Tj 2.372222 0 Td 48.148148 Tz (unfortunately, ) Tj 4.180556 0 Td 50.231481 Tz (as ) Tj 0.777778 0 Td 49.691358 Tz (the ) Tj 1.05 0 Td 45.046296 Tz (reactivity ) Tj 2.877778 0 Td 50.771605 Tz (within ) Tj 1.963889 0 Td 50.771605 Tz (the ) Tj 1.030556 0 Td 68.055556 Tz (human ) Tj 51.428571 0 0 51.428571 0 1657.767263 Tm 6.338889 0 Td 60.763889 Tz (body ) Tj 1.711111 0 Td 59.953704 Tz (of ) Tj 0.913889 0 Td 71.296296 Tz (LPA ) Tj 1.555556 0 Td 50.771605 Tz (within ) Tj 2.1 0 Td 46.759259 Tz (certain ) Tj 2.236111 0 Td 45.833333 Tz (tissues ) Tj 2.177778 0 Td 54.012346 Tz (has ) Tj 1.263889 0 Td 45.730453 Tz (resulted, ) Tj 2.722222 0 Td 46.990741 Tz (in ) Tj 0.816667 0 Td 48.148148 Tz (certain ) Tj 52.857143 0 0 52.857143 0 1620.217338 Tm 6.205405 0 Td 44.144144 Tz (studies, ) Tj 2.327027 0 Td 42.567568 Tz (in ) Tj 0.7 0 Td 52.202202 Tz (cancerous ) Tj 3.008108 0 Td 53.603604 Tz (growths ) Tj 2.421622 0 Td 63.851351 Tz (when ) Tj 1.721622 0 Td 48.648649 Tz (present ) Tj 2.213514 0 Td 44.144144 Tz (at ) Tj 0.681081 0 Td 45.495495 Tz (certain ) Tj 2.1 0 Td 42.342342 Tz (levels. ) Tj 51.428571 0 0 51.428571 0 1580.044335 Tm 6.377778 0 Td 48.611111 Tz (In ) Tj 0.738889 0 Td 43.75 Tz (this ) Tj 1.225 0 Td 55.092593 Tz (manner, ) Tj 2.488889 0 Td 47.314815 Tz (then, ) Tj 1.594444 0 Td 32.407407 Tz (it ) Tj 0.525 0 Td 54.012346 Tz (has ) Tj 1.108333 0 Td 57.523148 Tz (been ) Tj 1.555556 0 Td 50.411523 Tz (theorized ) Tj 2.858333 0 Td 46.990741 Tz (that ) Tj 1.263889 0 Td 48.611111 Tz (the ) Tj 1.011111 0 Td 49.074074 Tz (greater ) Tj 2.197222 0 Td 49.691358 Tz (the ) Tj 51.428571 0 0 51.428571 0 1542.915212 Tm 6.358333 0 Td 51.851852 Tz (incidence ) Tj 3.033333 0 Td 59.953704 Tz (of ) Tj 0.836111 0 Td 50.411523 Tz (autotaxin ) Tj 2.975 0 Td 44.965278 Tz (activity ) Tj 2.411111 0 Td 51.311728 Tz (within ) Tj 2.119444 0 Td 49.691358 Tz (the ) Tj 1.108333 0 Td 66.111111 Tz (human ) Tj 2.255556 0 Td 52.5 Tz (body, ) Tj 1.847222 0 Td 49.691358 Tz (the ) Tj 51.428571 0 0 51.428571 0 1507.206388 Tm 6.358333 0 Td 49.074074 Tz (greater ) Tj 2.236111 0 Td 48.611111 Tz (the ) Tj 1.030556 0 Td 45.959596 Tz (possibility ) Tj 3.208333 0 Td 59.953704 Tz (of ) Tj 0.855556 0 Td 70.216049 Tz (LPA ) Tj 1.458333 0 Td 48.905724 Tz (generation. ) Tj 3.422222 0 Td 84.259259 Tz (A ) Tj 0.7 0 Td 50.411523 Tz (reduction ) Tj 2.936111 0 Td 43.75 Tz (in ) Tj 0.738889 0 Td 49.691358 Tz (the ) Tj 51.428571 0 0 51.428571 0 1467.989899 Tm 6.358333 0 Td 45.37037 Tz (catalytic ) Tj 2.722222 0 Td 45.910494 Tz (capabilities ) Tj 3.558333 0 Td 61.574074 Tz (of ) Tj 0.875 0 Td 50.05144 Tz (autotaxin ) Tj 2.994444 0 Td 43.75 Tz (to ) Tj 0.797222 0 Td 51.388889 Tz (convert ) Tj 2.430556 0 Td 48.611111 Tz (the ) Tj 1.147222 0 Td 72.376543 Tz (LPC ) Tj 1.594444 0 Td 74.537037 Tz (mol ) Tj 51.428571 0 0 51.428571 0 1429.050292 Tm 6.358333 0 Td 51.203704 Tz (ecule ) Tj 1.652778 0 Td 45.37037 Tz (to ) Tj 0.7 0 Td 71.296296 Tz (LPA ) Tj 1.4 0 Td 60.277778 Tz (would ) Tj 1.886111 0 Td 46.866097 Tz (theoretically ) Tj 3.772222 0 Td 55.902778 Tz (permitan ) Tj 2.838889 0 Td 49.421296 Tz (ultimate ) Tj 2.508333 0 Td 50.771605 Tz (reduction ) Tj 51.428571 0 0 51.428571 0 1392.356718 Tm 6.358333 0 Td 45.37037 Tz (in ) Tj 0.719444 0 Td 45.959596 Tz (possibility ) Tj 3.208333 0 Td 58.333333 Tz (of ) Tj 0.777778 0 Td 59.143519 Tz (unwanted ) Tj 2.994444 0 Td 43.75 Tz (cell ) Tj 1.225 0 Td 46.367521 Tz (proliferation ) Tj 3.811111 0 Td 53.703704 Tz (through ) Tj 2.45 0 Td 55.092593 Tz (reduced ) Tj 51.428571 0 0 51.428571 0 1355.277247 Tm 6.377778 0 Td 71.296296 Tz (LPA ) Tj 1.477778 0 Td 53.472222 Tz (presence ) Tj 2.722222 0 Td 51.311728 Tz (within ) Tj 2.041667 0 Td 55.092593 Tz (a ) Tj 0.505556 0 Td 47.530864 Tz (subjects ) Tj 2.761111 0 Td 52.5 Tz (body. ) Tj 51.428571 0 0 51.428571 0 1314.601467 Tm 7.097222 0 Td 62.654321 Tz (The ) Tj 1.263889 0 Td 60.853909 Tz (mechanism ) Tj 3.422222 0 Td 55.092593 Tz (of ) Tj 0.738889 0 Td 50.05144 Tz (autotaxin ) Tj 2.838889 0 Td 55.092593 Tz (interms ) Tj 2.45 0 Td 53.472222 Tz (of ) Tj 0.719444 0 Td 55.452675 Tz (enzymatic ) Tj 3.130556 0 Td 45.37037 Tz (activity ) Tj 51.428571 0 0 51.428571 0 1274.091371 Tm 6.358333 0 Td 58.333333 Tz (and ) Tj 1.302778 0 Td 46.090535 Tz (catalysis ) Tj 2.761111 0 Td 43.75 Tz (to ) Tj 0.816667 0 Td 58.333333 Tz (form ) Tj 1.711111 0 Td 70.216049 Tz (LPA ) Tj 1.516667 0 Td 48.148148 Tz (resides ) Tj 2.275 0 Td 45.37037 Tz (in ) Tj 0.816667 0 Td 37.808642 Tz (its ) Tj 0.933333 0 Td 52.423747 Tz (phosphodiesterase ) Tj 51.428571 0 0 51.428571 0 1233.394366 Tm 6.358333 0 Td 45.075758 Tz (capability. ) Tj 3.286111 0 Td 71.296296 Tz (LPA ) Tj 1.536111 0 Td 56.17284 Tz (can ) Tj 1.283333 0 Td 56.712963 Tz (be ) Tj 0.933333 0 Td 52.572016 Tz (generated ) Tj 3.111111 0 Td 56.712963 Tz (from ) Tj 1.652778 0 Td 49.691358 Tz (the ) Tj 1.127778 0 Td 52.662037 Tz (cleavage ) Tj 2.780556 0 Td 59.953704 Tz (of ) Tj 0.875 0 Td 49.691358 Tz (the ) Tj 51.428571 0 0 51.428571 0 1191.037915 Tm 6.358333 0 Td 52.777778 Tz (phosphodiester ) Tj 4.530556 0 Td 57.685185 Tz (bonds ) Tj 1.847222 0 Td 56.712963 Tz (of ) Tj 0.758333 0 Td 60.763889 Tz (LPC, ) Tj 1.633333 0 Td 53.240741 Tz (through ) Tj 2.352778 0 Td 49.691358 Tz (the ) Tj 1.011111 0 Td 50.231481 Tz (function ) Tj 2.547222 0 Td 55.092593 Tz (of ) Tj 0.738889 0 Td 48.611111 Tz (a ) Tj 0.427778 0 Td 67.24537 Tz (phos ) Tj 51.428571 0 0 51.428571 0 1149.235294 Tm 6.358333 0 Td 51.851852 Tz (pholipase ) Tj 2.975 0 Td 63.194444 Tz (enzyme ) Tj 2.45 0 Td 49.907407 Tz (\(note ) Tj 1.711111 0 Td 57.407407 Tz (Formula ) Tj 2.625 0 Td 33.487654 Tz (I\). ) Tj 31.428571 0 0 31.428571 0 1034 Tm 35.35 0 Td 74.242424 Tz (Formula ) Tj 3.372727 0 Td 53.030303 Tz (I ) Tj 42.857143 0 0 42.857143 0 967 Tm 17.99 0 Td 83.611111 Tz (OH ) Tj 31.428571 0 0 31.428571 0 912 Tm 17.054545 0 Td 155.909091 Tz (O-P-O ) Tj 10.945455 0 Td 111.363636 Tz (O ) Tj 3.5 0 Td 169.69697 Tz (CH ) Tj 38.857143 0 0 38.857143 0 889.137255 Tm 8.389706 0 Td 128.063725 Tz (N1\)-N-1 ) Tj 9.238971 0 Td 209.099265 Tz (N1N1 ) Tj 8.466912 0 Td 36.458333 Tz (17 ) Tj 0.797794 0 Td 31.096814 Tz (l.23 ) Tj 2.238971 0 Td 85.784314 Tz (ATX ) Tj 51.428571 0 0 51.428571 0 841.061856 Tm 6.786111 0 Td 90.740741 Tz (/ ) Tj 0.777778 0 Td 87.5 Tz (\\ ) Tj 4.083333 0 Td 68.055556 Tz (OH ) Tj 31.428571 0 0 31.428571 0 817 Tm 29.75 0 Td 111.363636 Tz (O ) Tj 31.428571 0 0 31.428571 0 765 Tm 21.445455 0 Td 93.686869 Tz (LPC ) Tj 42.857143 0 0 42.857143 0 720 Tm 16.916667 0 Td 83.611111 Tz (OH ) Tj 53.809524 0 0 53.809524 0 633.301075 Tm 8.49292 0 Td 107.787611 Tz (to--o ) Tj 7.136283 0 Td 65.044248 Tz (O ) Tj 2.155752 0 Td 43.362832 Tz (C17H33 ) Tj 73.571429 0 0 73.571429 0 589.36 Tm 7.380583 0 Td 47.572816 Tz (OH ) Tj 4.825243 0 Td 131.391586 Tz (r ) Tj 31.428571 0 0 31.428571 0 561 Tm 28.604545 0 Td 111.363636 Tz (O ) Tj 31.428571 0 0 31.428571 0 508 Tm 23.004545 0 Td 93.686869 Tz (LPA ) Tj 31.428571 0 0 31.428571 0 329 Tm 33.345455 0 Td 65.151515 Tz (choline ) Tj 51.428571 0 0 51.428571 0 213.03079 Tm 6.377778 0 Td 48.611111 Tz (In ) Tj 1.011111 0 Td 46.616809 Tz (extracellular ) Tj 4.063889 0 Td 42.12963 Tz (fluids, ) Tj 2.216667 0 Td 42.939815 Tz (this ) Tj 1.458333 0 Td 55.092593 Tz (enzymatic ) Tj 3.383333 0 Td 46.8107 Tz (catalysis ) Tj 2.955556 0 Td 59.953704 Tz (of ) Tj 1.069444 0 Td 71.296296 Tz (LPC ) Tj 51.428571 0 0 51.428571 0 170.113402 Tm 6.358333 0 Td 57.87037 Tz (removes ) Tj 2.702778 0 Td 49.691358 Tz (the ) Tj 1.147222 0 Td 50.925926 Tz (choline ) Tj 2.372222 0 Td 52.391975 Tz (group, ) Tj 2.177778 0 Td 50 Tz (leaving ) Tj 2.391667 0 Td 59.953704 Tz (LPA, ) Tj 1.711111 0 Td 58.981481 Tz (which ) Tj 2.022222 0 Td 54.012346 Tz (has ) Tj 1.225 0 Td 55.092593 Tz (a ) Tj 0.583333 0 Td 62.654321 Tz (ten ) Tj 30 0 0 30 0 2547 Tm 41.666667 0 Td 75 Tz (10 ) Tj 30 0 0 30 0 2339 Tm 41.666667 0 Td 72.222222 Tz (15 ) Tj 30 0 0 30 0 1923 Tm 41.6 0 Td 77.777778 Tz (25 ) Tj 30 0 0 30 0 1716 Tm 41.6 0 Td 80.555556 Tz (30 ) Tj 30 0 0 30 0 1507 Tm 41.6 0 Td 77.777778 Tz (35 ) Tj 30 0 0 30 0 1299 Tm 41.566667 0 Td 83.333333 Tz (40 ) Tj 30 0 0 30 0 1091 Tm 41.566667 0 Td 80.555556 Tz (45 ) Tj 30 0 0 30 0 883 Tm 41.6 0 Td 80.555556 Tz (50 ) Tj 30 0 0 30 0 675 Tm 41.6 0 Td 77.777778 Tz (55 ) Tj 30 0 0 30 0 467 Tm 41.633333 0 Td 77.777778 Tz (60 ) Tj 30 0 0 30 0 259 Tm 41.633333 0 Td 75 Tz (65 ) Tj 51.428571 0 0 51.428571 0 2969 Tm 33.775 0 Td 74.537037 Tz (2 ) Tj 51.428571 0 0 51.428571 0 2916.907455 Tm 25.297222 0 Td 57.685185 Tz (dency ) Tj 1.963889 0 Td 46.990741 Tz (to ) Tj 0.836111 0 Td 49.331276 Tz (stimulate ) Tj 2.916667 0 Td 42.939815 Tz (cell ) Tj 1.283333 0 Td 56.712963 Tz (growth ) Tj 2.313889 0 Td 58.333333 Tz (and ) Tj 1.302778 0 Td 46.367521 Tz (proliferation ) Tj 3.888889 0 Td 48.611111 Tz (as ) Tj 0.855556 0 Td 51.851852 Tz (well ) Tj 1.497222 0 Td 50.231481 Tz (as ) Tj 51.428571 0 0 51.428571 0 2872.3 Tm 25.297222 0 Td 52.441077 Tz (chemotaxis. ) Tj 3.752778 0 Td 63.194444 Tz (From ) Tj 1.730556 0 Td 41.481481 Tz (this, ) Tj 1.477778 0 Td 32.407407 Tz (it ) Tj 0.583333 0 Td 52.777778 Tz (appears ) Tj 2.45 0 Td 45.37037 Tz (that ) Tj 1.283333 0 Td 50.771605 Tz (the ) Tj 1.147222 0 Td 46.990741 Tz (motility ) Tj 2.488889 0 Td 56.712963 Tz (of ) Tj 0.797222 0 Td 59.62963 Tz (tumor ) Tj 51.428571 0 0 51.428571 0 2829.626943 Tm 25.297222 0 Td 44.074074 Tz (cells ) Tj 1.613889 0 Td 38.888889 Tz (is ) Tj 0.738889 0 Td 51.131687 Tz (increased ) Tj 3.013889 0 Td 50.231481 Tz (as ) Tj 0.875 0 Td 47.962963 Tz (well, ) Tj 1.730556 0 Td 46.8107 Tz (resulting ) Tj 2.780556 0 Td 46.990741 Tz (in ) Tj 0.836111 0 Td 48.287037 Tz (properties ) Tj 3.188889 0 Td 58.333333 Tz (and ) Tj 1.322222 0 Td 57.523148 Tz (gene ) Tj 51.428571 0 0 51.428571 0 2783.54933 Tm 25.297222 0 Td 51.527778 Tz (expression ) Tj 3.305556 0 Td 51.311728 Tz (within ) Tj 2.080556 0 Td 46.296296 Tz (certain ) Tj 2.158333 0 Td 55.092593 Tz (carcinomas ) Tj 3.538889 0 Td 51.851852 Tz (\(Such ) Tj 1.75 0 Td 44.290123 Tz (as, ) Tj 1.011111 0 Td 48.611111 Tz (for ) Tj 1.05 0 Td 47.170782 Tz (instance, ) Tj 51.428571 0 0 51.428571 0 2741.713043 Tm 25.277778 0 Td 49.151235 Tz (breast ) Tj 1.983333 0 Td 54.012346 Tz (cancer ) Tj 2.138889 0 Td 41.666667 Tz (cells\), ) Tj 2.022222 0 Td 52.314815 Tz (causing ) Tj 2.430556 0 Td 48.148148 Tz (further ) Tj 2.216667 0 Td 51.851852 Tz (processing ) Tj 3.344444 0 Td 46.990741 Tz (into ) Tj 1.380556 0 Td 55.092593 Tz (a ) Tj 0.563889 0 Td 58.333333 Tz (form ) Tj 51.428571 0 0 51.428571 0 2698.184178 Tm 25.277778 0 Td 46.990741 Tz (that ) Tj 1.380556 0 Td 38.888889 Tz (is ) Tj 0.7 0 Td 49.331276 Tz (bioactive ) Tj 2.897222 0 Td 60.493827 Tz (and ) Tj 1.302778 0 Td 47.43266 Tz (potentially ) Tj 3.402778 0 Td 52.175926 Tz (dangerous. ) Tj 3.422222 0 Td 50.555556 Tz (Metastasis ) Tj 3.305556 0 Td 60.493827 Tz (and ) Tj 51.428571 0 0 51.428571 0 2653.993412 Tm 25.297222 0 Td 53.619529 Tz (oncogenesis ) Tj 3.869444 0 Td 58.333333 Tz (of ) Tj 0.933333 0 Td 52.391975 Tz (cancer ) Tj 2.197222 0 Td 44.074074 Tz (cells ) Tj 1.613889 0 Td 55.092593 Tz (appear ) Tj 2.275 0 Td 43.75 Tz (to ) Tj 0.875 0 Td 55.092593 Tz (occur ) Tj 1.925 0 Td 50.231481 Tz (as ) Tj 0.913889 0 Td 51.851852 Tz (well ) Tj 1.575 0 Td 54.282407 Tz (with ) Tj 51.428571 0 0 51.428571 0 2611.536618 Tm 25.297222 0 Td 49.826389 Tz (elevated ) Tj 2.761111 0 Td 45.37037 Tz (levels ) Tj 2.002778 0 Td 59.953704 Tz (of ) Tj 1.011111 0 Td 70.216049 Tz (LPA ) Tj 1.594444 0 Td 50.925926 Tz (present ) Tj 2.508333 0 Td 50.771605 Tz (within ) Tj 2.197222 0 Td 51.851852 Tz (a ) Tj 0.680556 0 Td 48.611111 Tz (targeted ) Tj 2.702778 0 Td 47.222222 Tz (region. ) Tj 51.428571 0 0 51.428571 0 2565.55122 Tm 25.316667 0 Td 51.49177 Tz (Increased ) Tj 2.916667 0 Td 77.777778 Tz (ATX ) Tj 1.575 0 Td 51.527778 Tz (expression ) Tj 3.286111 0 Td 52.932099 Tz (has ) Tj 1.147222 0 Td 56.712963 Tz (been ) Tj 1.575 0 Td 45.694444 Tz (identified ) Tj 2.916667 0 Td 45.37037 Tz (in ) Tj 0.758333 0 Td 46.666667 Tz (renal ) Tj 1.594444 0 Td 55.740741 Tz (carci ) Tj 51.428571 0 0 51.428571 0 2522.269368 Tm 25.297222 0 Td 59.62963 Tz (noma, ) Tj 2.002778 0 Td 48.611111 Tz (metastatic ) Tj 3.091667 0 Td 48.611111 Tz (breast ) Tj 1.925 0 Td 48.611111 Tz (cancer, ) Tj 2.236111 0 Td 50 Tz (thyroid ) Tj 2.294444 0 Td 53.148148 Tz (carcinoma, ) Tj 3.422222 0 Td 60.185185 Tz (Hodgkin ) Tj 51.428571 0 0 51.428571 0 2480.44352 Tm 25.297222 0 Td 60.493827 Tz (lymphoma, ) Tj 3.441667 0 Td 59.41358 Tz (and ) Tj 1.205556 0 Td 49.421296 Tz (invasive ) Tj 2.508333 0 Td 52.391975 Tz (glioblastoma ) Tj 3.966667 0 Td 51.557239 Tz (multiforme, ) Tj 3.538889 0 Td 51.851852 Tz (as ) Tj 0.797222 0 Td 51.851852 Tz (well ) Tj 1.4 0 Td 50.231481 Tz (as ) Tj 51.428571 0 0 51.428571 0 2436.542056 Tm 25.297222 0 Td 50.555556 Tz (other ) Tj 1.633333 0 Td 47.170782 Tz (diseases, ) Tj 2.683333 0 Td 50.771605 Tz (including ) Tj 2.897222 0 Td 49.826389 Tz (multiple ) Tj 2.527778 0 Td 44.398148 Tz (Sclerosis, ) Tj 2.8 0 Td 46.585648 Tz (obesity, ) Tj 2.352778 0 Td 47.170782 Tz (diabetes, ) Tj 51.428571 0 0 51.428571 0 2390.052252 Tm 25.297222 0 Td 54.208754 Tz (Alzheimer's ) Tj 3.791667 0 Td 47.170782 Tz (diseases, ) Tj 2.722222 0 Td 59.41358 Tz (and ) Tj 1.244444 0 Td 51.851852 Tz (chronic ) Tj 2.352778 0 Td 47.314815 Tz (pain. ) Tj 51.428571 0 0 51.428571 0 2348.230179 Tm 26.036111 0 Td 37.268519 Tz (It ) Tj 0.563889 0 Td 54.012346 Tz (has ) Tj 1.127778 0 Td 50.231481 Tz (thus ) Tj 1.361111 0 Td 56.712963 Tz (been ) Tj 1.536111 0 Td 54.444444 Tz (determined ) Tj 3.402778 0 Td 45.37037 Tz (that ) Tj 1.244444 0 Td 48.611111 Tz (the ) Tj 0.991667 0 Td 44.907407 Tz (ability ) Tj 2.022222 0 Td 46.990741 Tz (to ) Tj 0.7 0 Td 49.016204 Tz (prevent, ) Tj 2.488889 0 Td 53.472222 Tz (or ) Tj 0.758333 0 Td 45.37037 Tz (at ) Tj 51.428571 0 0 51.428571 0 2302.711538 Tm 25.297222 0 Td 44.722222 Tz (least ) Tj 1.497222 0 Td 49.074074 Tz (reduce, ) Tj 2.216667 0 Td 49.691358 Tz (the ) Tj 0.991667 0 Td 61.574074 Tz (amount ) Tj 2.333333 0 Td 55.092593 Tz (of ) Tj 0.738889 0 Td 71.296296 Tz (LPA ) Tj 1.438889 0 Td 50.771605 Tz (within ) Tj 1.963889 0 Td 49.691358 Tz (the ) Tj 0.991667 0 Td 66.111111 Tz (human ) Tj 2.138889 0 Td 59.953704 Tz (body ) Tj 1.575 0 Td 52.5 Tz (holds ) Tj 51.428571 0 0 51.428571 0 2263.089987 Tm 25.297222 0 Td 47.962963 Tz (great ) Tj 1.711111 0 Td 56.018519 Tz (promise ) Tj 2.625 0 Td 38.888889 Tz (at, ) Tj 0.991667 0 Td 47.170782 Tz (likewise, ) Tj 2.838889 0 Td 50.05144 Tz (reducing, ) Tj 2.994444 0 Td 42.12963 Tz (if ) Tj 0.719444 0 Td 50.771605 Tz (not ) Tj 1.147222 0 Td 49.494949 Tz (preventing, ) Tj 3.538889 0 Td 50.771605 Tz (the ) Tj 51.428571 0 0 51.428571 0 2216.791325 Tm 25.297222 0 Td 51.851852 Tz (onset ) Tj 1.672222 0 Td 51.851852 Tz (of ) Tj 0.680556 0 Td 47.685185 Tz (certain ) Tj 2.1 0 Td 47.530864 Tz (diseases, ) Tj 2.722222 0 Td 57.523148 Tz (most ) Tj 1.458333 0 Td 51.58179 Tz (prominently, ) Tj 3.830556 0 Td 47.222222 Tz (certain ) Tj 2.1 0 Td 48.206019 Tz (cancers. ) Tj 2.469444 0 Td 37.268519 Tz (It ) Tj 48.571429 0 0 48.571429 0 2173 Tm 26.764706 0 Td 57.189542 Tz (has ) Tj 1.255882 0 Td 60.04902 Tz (been ) Tj 1.647059 0 Td 50.784314 Tz (theorized, ) Tj 3.252941 0 Td 53.186275 Tz (as ) Tj 0.885294 0 Td 56.27451 Tz (noted ) Tj 1.873529 0 Td 56.045752 Tz (above, ) Tj 2.223529 0 Td 48.039216 Tz (that ) Tj 1.338235 0 Td 52.995643 Tz (autotaxin ) Tj 3.129412 0 Td 60.477941 Tz (modifica ) Tj 51.428571 0 0 51.428571 0 2128.763224 Tm 25.277778 0 Td 47.314815 Tz (tions ) Tj 1.691667 0 Td 68.055556 Tz (may ) Tj 1.458333 0 Td 51.851852 Tz (prevent ) Tj 2.430556 0 Td 48.611111 Tz (the ) Tj 1.127778 0 Td 50.673401 Tz (undesirable ) Tj 3.558333 0 Td 52.824074 Tz (conversion ) Tj 3.422222 0 Td 57.523148 Tz (from ) Tj 1.691667 0 Td 72.376543 Tz (LPC ) Tj 1.536111 0 Td 45.37037 Tz (to ) Tj 51.428571 0 0 51.428571 0 2087.737226 Tm 25.316667 0 Td 60.763889 Tz (LPA; ) Tj 1.633333 0 Td 49.691358 Tz (the ) Tj 1.011111 0 Td 43.981481 Tz (ability ) Tj 2.022222 0 Td 45.37037 Tz (to ) Tj 0.680556 0 Td 48.611111 Tz (actually ) Tj 2.469444 0 Td 54.768519 Tz (accomplish ) Tj 3.461111 0 Td 53.472222 Tz (such ) Tj 1.458333 0 Td 55.092593 Tz (a ) Tj 0.486111 0 Td 44.830247 Tz (result ) Tj 1.730556 0 Td 54.012346 Tz (has ) Tj 1.108333 0 Td 59.143519 Tz (been ) Tj 51.428571 0 0 51.428571 0 2042.336538 Tm 25.297222 0 Td 45.775463 Tz (elusive, ) Tj 2.333333 0 Td 54.6875 Tz (however, ) Tj 2.761111 0 Td 43.75 Tz (at ) Tj 0.680556 0 Td 44.074074 Tz (least ) Tj 1.458333 0 Td 45.37037 Tz (to ) Tj 0.719444 0 Td 48.611111 Tz (the ) Tj 0.991667 0 Td 54.012346 Tz (degree ) Tj 2.1 0 Td 51.49177 Tz (necessary ) Tj 2.955556 0 Td 47.530864 Tz (for ) Tj 0.972222 0 Td 46.450617 Tz (effective ) Tj 51.428571 0 0 51.428571 0 1996.616891 Tm 25.277778 0 Td 51.262626 Tz (broad-scale ) Tj 3.616667 0 Td 44.486532 Tz (utilization ) Tj 3.169444 0 Td 59.953704 Tz (of ) Tj 0.875 0 Td 54.282407 Tz (Such ) Tj 1.516667 0 Td 58.333333 Tz (a ) Tj 0.622222 0 Td 54.62963 Tz (method. ) Tj 2.527778 0 Td 68.055556 Tz (Any ) Tj 1.497222 0 Td 51.041667 Tz (modification ) Tj 51.428571 0 0 51.428571 0 1955.406739 Tm 25.277778 0 Td 51.388889 Tz (thereof ) Tj 2.255556 0 Td 58.333333 Tz (must ) Tj 1.516667 0 Td 48.611111 Tz (exhibit ) Tj 2.177778 0 Td 56.712963 Tz (an ) Tj 0.836111 0 Td 44.444444 Tz (ability ) Tj 2.022222 0 Td 46.990741 Tz (to ) Tj 0.738889 0 Td 45.37037 Tz (drastically ) Tj 3.188889 0 Td 52.932099 Tz (reduce ) Tj 2.061111 0 Td 50.771605 Tz (the ) Tj 1.05 0 Td 54.444444 Tz (activ ) Tj 51.428571 0 0 51.428571 0 1912.493671 Tm 25.297222 0 Td 42.12963 Tz (ity ) Tj 1.030556 0 Td 59.953704 Tz (of ) Tj 0.894444 0 Td 49.691358 Tz (autotaxin ) Tj 2.994444 0 Td 53.148148 Tz (while ) Tj 1.847222 0 Td 45.37037 Tz (also, ) Tj 1.652778 0 Td 49.583333 Tz (preferably ) Tj 3.227778 0 Td 49.583333 Tz (exhibiting ) Tj 3.247222 0 Td 46.180556 Tz (oral ) Tj 1.380556 0 Td 65.895062 Tz (bio ) Tj 51.428571 0 0 51.428571 0 1870.918519 Tm 25.297222 0 Td 44.830247 Tz (availability ) Tj 3.402778 0 Td 51.851852 Tz (as ) Tj 0.816667 0 Td 46.666667 Tz (well. ) Tj 51.428571 0 0 51.428571 0 1823.542553 Tm 26.016667 0 Td 53.652263 Tz (Autotaxin ) Tj 3.227778 0 Td 60.277778 Tz (\(ATX, ) Tj 2.119444 0 Td 64.814815 Tz (NPP2\) ) Tj 2.255556 0 Td 60.493827 Tz (was ) Tj 1.380556 0 Td 46.990741 Tz (originally ) Tj 3.130556 0 Td 46.018519 Tz (identified ) Tj 3.033333 0 Td 48.611111 Tz (as ) Tj 0.894444 0 Td 59.953704 Tz (an ) Tj 51.428571 0 0 51.428571 0 1779.128954 Tm 25.297222 0 Td 50.411523 Tz (autocrine ) Tj 2.936111 0 Td 46.990741 Tz (motility ) Tj 2.488889 0 Td 46.990741 Tz (factor ) Tj 1.847222 0 Td 46.990741 Tz (in ) Tj 0.777778 0 Td 49.691358 Tz (the ) Tj 1.069444 0 Td 52.146465 Tz (conditioned ) Tj 3.655556 0 Td 58.333333 Tz (media ) Tj 1.925 0 Td 58.333333 Tz (of ) Tj 0.777778 0 Td 65.462963 Tz (A2058 ) Tj 51.428571 0 0 51.428571 0 1737.169492 Tm 25.297222 0 Td 63.194444 Tz (melanoma ) Tj 3.344444 0 Td 41.049383 Tz (cells. ) Tj 1.808333 0 Td 51.851852 Tz (Subsequently, ) Tj 4.336111 0 Td 76.697531 Tz (ATX ) Tj 1.711111 0 Td 61.574074 Tz (was ) Tj 1.438889 0 Td 61.574074 Tz (shown ) Tj 2.177778 0 Td 45.37037 Tz (to ) Tj 0.855556 0 Td 48.611111 Tz (be, ) Tj 1.186111 0 Td 50.231481 Tz (as ) Tj 51.428571 0 0 51.428571 0 1695.917073 Tm 25.297222 0 Td 51.851852 Tz (discussed ) Tj 3.033333 0 Td 52.932099 Tz (above, ) Tj 2.138889 0 Td 51.851852 Tz (the ) Tj 1.186111 0 Td 52.614379 Tz (lysophospholipase ) Tj 5.638889 0 Td 84.259259 Tz (D ) Tj 0.758333 0 Td 63.194444 Tz (enzyme ) Tj 2.547222 0 Td 59.953704 Tz (respon ) Tj 51.428571 0 0 51.428571 0 1653.301176 Tm 25.316667 0 Td 44.722222 Tz (sible ) Tj 1.497222 0 Td 47.530864 Tz (for ) Tj 0.952778 0 Td 48.971193 Tz (synthesis ) Tj 2.761111 0 Td 56.712963 Tz (of ) Tj 0.758333 0 Td 49.691358 Tz (the ) Tj 1.011111 0 Td 48.611111 Tz (bioactive ) Tj 2.761111 0 Td 44.074074 Tz (lipid ) Tj 1.438889 0 Td 51.244213 Tz (lysophosphatidic ) Tj 5.055556 0 Td 51.851852 Tz (acid ) Tj 51.428571 0 0 51.428571 0 1609.118765 Tm 25.316667 0 Td 59.62963 Tz (\(LPA\) ) Tj 1.886111 0 Td 45.37037 Tz (in ) Tj 0.719444 0 Td 46.018519 Tz (vivo. ) Tj 1.536111 0 Td 46.090535 Tz (Specific, ) Tj 2.605556 0 Td 51.311728 Tz (potent ) Tj 1.944444 0 Td 46.342593 Tz (inhibitors ) Tj 2.916667 0 Td 53.472222 Tz (of ) Tj 0.719444 0 Td 75.617284 Tz (ATX ) Tj 1.497222 0 Td 49.691358 Tz (are ) Tj 0.991667 0 Td 48.971193 Tz (therefore ) Tj 51.428571 0 0 51.428571 0 1567.666667 Tm 25.297222 0 Td 48.251029 Tz (desirable ) Tj 2.780556 0 Td 51.851852 Tz (as ) Tj 0.836111 0 Td 52.5 Tz (novel ) Tj 1.75 0 Td 48.905724 Tz (therapeutic ) Tj 3.422222 0 Td 45.910494 Tz (leads. ) Tj 51.428571 0 0 51.428571 0 1528.785805 Tm 26.036111 0 Td 59.143519 Tz (Examples ) Tj 3.052778 0 Td 58.333333 Tz (of ) Tj 0.816667 0 Td 53.148148 Tz (metal ) Tj 1.808333 0 Td 46.666667 Tz (chelators, ) Tj 3.013889 0 Td 44.074074 Tz (lipid ) Tj 1.497222 0 Td 53.240741 Tz (analogs ) Tj 2.430556 0 Td 59.41358 Tz (and ) Tj 1.302778 0 Td 46.342593 Tz (non-lipid, ) Tj 40 0 0 40 0 1490 Tm 32.55 0 Td 66.666667 Tz (small ) Tj 2.275 0 Td 69.444444 Tz (molecules ) Tj 3.975 0 Td 73.958333 Tz (have ) Tj 2 0 Td 51.388889 Tz (all ) Tj 1.175 0 Td 72.916667 Tz (been ) Tj 2 0 Td 59.166667 Tz (identified ) Tj 3.75 0 Td 62.5 Tz (as ) Tj 1.025 0 Td 64.351852 Tz (autotaxin ) Tj 3.725 0 Td 69.444444 Tz (inhibi ) Tj 51.428571 0 0 51.428571 0 1442.395887 Tm 25.277778 0 Td 42.12963 Tz (tors. ) Tj 1.633333 0 Td 55.740741 Tz (Metal ) Tj 1.983333 0 Td 49.331276 Tz (chelators ) Tj 2.975 0 Td 55.092593 Tz (such ) Tj 1.652778 0 Td 50.231481 Tz (as ) Tj 0.991667 0 Td 66.111111 Tz (EDTA, ) Tj 2.333333 0 Td 50.339506 Tz (phenanthroline, ) Tj 4.841667 0 Td 60.493827 Tz (and ) Tj 51.428571 0 0 51.428571 0 1401.30622 Tm 25.316667 0 Td 48.316498 Tz (L-histidine ) Tj 3.325 0 Td 55.092593 Tz (have ) Tj 1.477778 0 Td 56.712963 Tz (been ) Tj 1.536111 0 Td 61.574074 Tz (shown ) Tj 2.002778 0 Td 46.990741 Tz (to ) Tj 0.738889 0 Td 44.907407 Tz (inhibit ) Tj 2.002778 0 Td 77.777778 Tz (ATX ) Tj 1.516667 0 Td 42.849794 Tz (activity, ) Tj 2.469444 0 Td 65.895062 Tz (presum ) Tj 51.428571 0 0 51.428571 0 1357.683578 Tm 25.297222 0 Td 51.851852 Tz (ably ) Tj 1.633333 0 Td 45.37037 Tz (via ) Tj 1.205556 0 Td 46.990741 Tz (interactions ) Tj 3.733333 0 Td 52.662037 Tz (with ) Tj 1.633333 0 Td 48.070988 Tz (active ) Tj 2.061111 0 Td 42.939815 Tz (site ) Tj 1.361111 0 Td 48.611111 Tz (divalent ) Tj 2.702778 0 Td 51.851852 Tz (metal ) Tj 1.925 0 Td 50.231481 Tz (ions ) Tj 51.428571 0 0 51.428571 0 1321.689345 Tm 25.297222 0 Td 50.636574 Tz (required ) Tj 2.761111 0 Td 48.611111 Tz (for ) Tj 1.186111 0 Td 47.530864 Tz (function. ) Tj 2.955556 0 Td 51.203704 Tz (Lipid ) Tj 1.866667 0 Td 52.777778 Tz (analogs ) Tj 2.566667 0 Td 49.331276 Tz (represent ) Tj 2.955556 0 Td 51.851852 Tz (the ) Tj 1.263889 0 Td 45.833333 Tz (largest ) Tj 51.428571 0 0 51.428571 0 1276.056581 Tm 25.297222 0 Td 56.388889 Tz (group ) Tj 1.847222 0 Td 59.953704 Tz (of ) Tj 0.855556 0 Td 49.421296 Tz (reported ) Tj 2.508333 0 Td 78.858025 Tz (ATX ) Tj 1.613889 0 Td 46.342593 Tz (inhibitors ) Tj 2.936111 0 Td 49.421296 Tz (\(see ) Tj 1.4 0 Td 52.662037 Tz (FIG. ) Tj 1.516667 0 Td 48.611111 Tz (1 ) Tj 0.525 0 Td 47.530864 Tz (for ) Tj 1.011111 0 Td 44.830247 Tz (structures\). ) Tj 51.428571 0 0 51.428571 0 1237.125301 Tm 25.316667 0 Td 71.296296 Tz (LPA ) Tj 1.458333 0 Td 59.41358 Tz (and ) Tj 1.244444 0 Td 48.611111 Tz (the ) Tj 1.088889 0 Td 46.296296 Tz (related ) Tj 2.119444 0 Td 48.971193 Tz (bioactive ) Tj 2.838889 0 Td 44.074074 Tz (lipid ) Tj 1.477778 0 Td 53.030303 Tz (sphingosine ) Tj 3.733333 0 Td 53.030303 Tz (1-phosphate ) Tj 51.428571 0 0 51.428571 0 1192.520581 Tm 25.316667 0 Td 54.444444 Tz (\(S1P\) ) Tj 1.827778 0 Td 58.333333 Tz (were ) Tj 1.555556 0 Td 50.87963 Tz (previously ) Tj 3.208333 0 Td 62.222222 Tz (shown ) Tj 2.041667 0 Td 45.37037 Tz (to ) Tj 0.738889 0 Td 49.826389 Tz (function ) Tj 2.566667 0 Td 50.231481 Tz (as ) Tj 0.797222 0 Td 54.6875 Tz (feedback ) Tj 2.761111 0 Td 54.012346 Tz (inhibi ) Tj 51.428571 0 0 51.428571 0 1151.553398 Tm 25.277778 0 Td 46.180556 Tz (tors ) Tj 1.225 0 Td 56.712963 Tz (of ) Tj 0.758333 0 Td 64.00463 Tz (ATX. ) Tj 1.691667 0 Td 52.662037 Tz (This ) Tj 1.438889 0 Td 51.49177 Tz (discovery ) Tj 2.916667 0 Td 49.691358 Tz (led ) Tj 1.05 0 Td 43.75 Tz (to ) Tj 0.680556 0 Td 49.691358 Tz (the ) Tj 1.030556 0 Td 48.611111 Tz (analysis ) Tj 2.45 0 Td 58.333333 Tz (of ) Tj 0.777778 0 Td 48.148148 Tz (several ) Tj 2.197222 0 Td 71.296296 Tz (LPA ) Tj 51.428571 0 0 51.428571 0 1111.667506 Tm 25.297222 0 Td 58.333333 Tz (and ) Tj 1.302778 0 Td 63.734568 Tz (S1P ) Tj 1.361111 0 Td 53.240741 Tz (analogs ) Tj 2.488889 0 Td 48.611111 Tz (as ) Tj 0.797222 0 Td 77.777778 Tz (ATX ) Tj 1.672222 0 Td 43.897306 Tz (inhibitors. ) Tj 3.227778 0 Td 54.6875 Tz (Reported ) Tj 2.877778 0 Td 71.296296 Tz (LPA ) Tj 1.516667 0 Td 52.777778 Tz (analogs ) Tj 51.428571 0 0 51.428571 0 1070.379352 Tm 25.297222 0 Td 50.925926 Tz (include ) Tj 2.391667 0 Td 42.777778 Tz (fatty ) Tj 1.497222 0 Td 51.388889 Tz (alcohol ) Tj 2.372222 0 Td 51.851852 Tz (phosphates, ) Tj 3.675 0 Td 56.17284 Tz (Darmstoff ) Tj 3.15 0 Td 50.636574 Tz (analogs, ) Tj 2.644444 0 Td 48.070988 Tz (cyclic ) Tj 51.428571 0 0 51.428571 0 1030.057247 Tm 25.297222 0 Td 51.58179 Tz (phosphatidic ) Tj 4.025 0 Td 50.231481 Tz (acid ) Tj 1.497222 0 Td 50.231481 Tz (analogs, ) Tj 2.702778 0 Td 59.41358 Tz (and ) Tj 1.341667 0 Td 55.092593 Tz (phosphonates ) Tj 4.277778 0 Td 59.953704 Tz (\(VPC8a202, ) Tj 51.428571 0 0 51.428571 0 985.337079 Tm 25.316667 0 Td 56.481481 Tz (S32826, ) Tj 2.644444 0 Td 59.41358 Tz (and ) Tj 1.302778 0 Td 59.722222 Tz (JGW-8\). ) Tj 2.780556 0 Td 68.055556 Tz (One ) Tj 1.497222 0 Td 50.231481 Tz (reported ) Tj 2.683333 0 Td 64.814815 Tz (S1P ) Tj 1.419444 0 Td 50.925926 Tz (analog, ) Tj 2.430556 0 Td 74.537037 Tz (FTY720 ) Tj 51.428571 0 0 51.428571 0 943.708223 Tm 25.297222 0 Td 52.175926 Tz (phosphate, ) Tj 3.480556 0 Td 54.012346 Tz (has ) Tj 1.322222 0 Td 48.611111 Tz (also ) Tj 1.536111 0 Td 56.712963 Tz (been ) Tj 1.691667 0 Td 59.143519 Tz (examined ) Tj 3.188889 0 Td 50.231481 Tz (as ) Tj 0.972222 0 Td 55.092593 Tz (an ) Tj 1.011111 0 Td 77.777778 Tz (ATX ) Tj 1.769444 0 Td 46.8107 Tz (inhibitor ) Tj 51.428571 0 0 51.428571 0 903.480841 Tm 25.316667 0 Td 45.959596 Tz (\(structures ) Tj 3.286111 0 Td 59.953704 Tz (of ) Tj 0.875 0 Td 49.907407 Tz (these ) Tj 1.75 0 Td 49.907407 Tz (types ) Tj 1.75 0 Td 59.953704 Tz (of ) Tj 0.836111 0 Td 52.662037 Tz (previous ) Tj 2.722222 0 Td 77.777778 Tz (ATX ) Tj 1.672222 0 Td 46.990741 Tz (inhibiting ) Tj 3.033333 0 Td 84.259259 Tz (com ) Tj 51.428571 0 0 51.428571 0 862.816121 Tm 25.297222 0 Td 57.79321 Tz (pounds ) Tj 2.275 0 Td 49.691358 Tz (are ) Tj 1.069444 0 Td 53.472222 Tz (provided ) Tj 2.741667 0 Td 51.851852 Tz (below\). ) Tj 42.857143 0 0 42.857143 0 743 Tm 40.81 0 Td 83.611111 Tz (OH ) Tj 46.285714 0 0 46.285714 0 682.666667 Tm 33.574074 0 Td 104.423868 Tz (V ) Tj 1.728395 0 Td 75.617284 Tz (O ) Tj 2.570988 0 Td 39.609053 Tz (s ) Tj 2.398148 0 Td 75.617284 Tz (O ) Tj 2.549383 0 Td 61.213992 Tz (R ) Tj 52.857143 0 0 52.857143 0 615 Tm 28.340541 0 Td 73.573574 Tz (HO1 ) Tj 1.759459 0 Td 75.675676 Tz (V ) Tj 31.428571 0 0 31.428571 0 590 Tm 51.195455 0 Td 111.363636 Tz (OH ) Tj 9.959091 0 Td 111.363636 Tz (O ) Tj 40 0 0 40 0 529.24282 Tm 38.575 0 Td 53.90625 Tz (Lysophosphatidic ) Tj 5.375 0 Td 45.833333 Tz (acid, ) Tj 1.6 0 Td 83.333333 Tz (R ) Tj 0.65 0 Td 66.666667 Tz (= ) Tj 0.55 0 Td 59.027778 Tz (C17H33 ) Tj 31.428571 0 0 31.428571 0 489 Tm 49.095455 0 Td 111.363636 Tz (O ) Tj 52.857143 0 0 52.857143 0 454 Tm 29.418919 0 Td 88.288288 Tz (V ) Tj 57.142857 0 0 57.142857 0 414 Tm 27.1075 0 Td 72.916667 Tz (- ) Tj 52.857143 0 0 52.857143 0 396 Tm 28.359459 0 Td 70.42042 Tz (HO1 ) Tj 1.759459 0 Td 66.216216 Tz (M ) Tj 31.428571 0 0 31.428571 0 374 Tm 51.195455 0 Td 111.363636 Tz (OH ) Tj 31.428571 0 0 31.428571 0 432 Tm 61.154545 0 Td 111.363636 Tz (O ) Tj 58.571429 0 0 58.571429 0 342.871287 Tm 31.82439 0 Td 65.447154 Tz (N ) Tj 0.478049 0 Td 173.577236 Tz (l ) Tj 1.536585 0 Td 48.373984 Tz (R ) Tj 31.428571 0 0 31.428571 0 310 Tm 59.404545 0 Td 106.060606 Tz (H ) Tj 40 0 0 40 0 256.525038 Tm 35.4 0 Td 54.495614 Tz (4-\(tetradecanoylamino\)benzylphosphonic ) Tj 12.6 0 Td 50 Tz (acid ) Tj 1.425 0 Td 52.777778 Tz (\(S32826\), ) Tj 38.571429 0 0 38.571429 0 218 Tm 43.607407 0 Td 82.098765 Tz (R ) Tj 0.674074 0 Td 73.45679 Tz (= ) Tj 0.622222 0 Td 72.592593 Tz (C3H27 ) Tj ET Q endstream endobj 282 0 obj << /Length 1 >> stream q endstream endobj 283 0 obj << /Length 17625 >> stream Q q 0.24 0 0 0.24 0 0 cm BT /F1 1 Tf 3 Tr 62.857143 0 0 62.857143 0 3023 Tm 17.325 0 Td 83.522727 Tz (US ) Tj 1.240909 0 Td 57.154882 Tz (8,497,371 ) Tj 3.388636 0 Td 74.242424 Tz (B2 ) Tj 52.857143 0 0 52.857143 0 2968 Tm 14.454054 0 Td 72.522523 Tz (3 ) Tj 40 0 0 40 0 2913 Tm 17.475 0 Td 67.083333 Tz (-continued ) Tj 31.428571 0 0 31.428571 0 2887 Tm 22.718182 0 Td 111.363636 Tz (X ) Tj 58.571429 0 0 58.571429 0 2845 Tm 12.412195 0 Td 91.768293 Tz (W-YS ) Tj 31.428571 0 0 31.428571 0 2822.285714 Tm 22.909091 0 Td 63.636364 Tz (1. ) Tj 0.954545 0 Td 79.545455 Tz (P ) Tj 3.627273 0 Td 90.151515 Tz (R ) Tj 51.428571 0 0 51.428571 0 2794 Tm 13.027778 0 Td 69.135802 Tz (HO1 ) Tj 1.808333 0 Td 71.296296 Tz (M ) Tj 31.428571 0 0 31.428571 0 2772 Tm 24.818182 0 Td 111.363636 Tz (OH ) Tj 40 0 0 40 0 2715.935714 Tm 11.425 0 Td 50 Tz (Fatty ) Tj 1.675 0 Td 49.166667 Tz (alkyl ) Tj 1.65 0 Td 53.819444 Tz (phosphonate, ) Tj 4.05 0 Td 91.666667 Tz (X ) Tj 0.725 0 Td 70.833333 Tz (= ) Tj 0.55 0 Td 60.416667 Tz (O, ) Tj 0.9 0 Td 95.833333 Tz (Y ) Tj 0.75 0 Td 66.666667 Tz (= ) Tj 0.55 0 Td 61.458333 Tz (CH2, ) Tj 1.725 0 Td 79.166667 Tz (R ) Tj 0.65 0 Td 66.666667 Tz (= ) Tj 0.55 0 Td 70.833333 Tz (C3H27 ) Tj 40 0 0 40 0 2682.256831 Tm 11.575 0 Td 50 Tz (Fatty ) Tj 1.65 0 Td 52.192982 Tz (alkylthiophosphate, ) Tj 6.1 0 Td 95.833333 Tz (X ) Tj 0.775 0 Td 66.666667 Tz (= ) Tj 0.55 0 Td 50 Tz (S, ) Tj 0.975 0 Td 91.666667 Tz (Y ) Tj 0.725 0 Td 66.666667 Tz (= ) Tj 0.55 0 Td 60.416667 Tz (O, ) Tj 0.925 0 Td 83.333333 Tz (R ) Tj 0.65 0 Td 70.833333 Tz (= ) Tj 0.6 0 Td 58.333333 Tz (C18H35 ) Tj 37.142857 0 0 37.142857 0 2640.625 Tm 17.796154 0 Td 94.230769 Tz (X ) Tj 3.069231 0 Td 96.474359 Tz (OH ) Tj 150 0 0 150 0 2504 Tm 5.213333 0 Td 90.740741 Tz (N-- ) Tj 31.428571 0 0 31.428571 0 2485 Tm 20.204545 0 Td 111.363636 Tz (OH ) Tj 9.990909 0 Td 111.363636 Tz (O ) Tj 40 0 0 40 0 2434.015656 Tm 12.675 0 Td 50.980392 Tz (Alpha-substituted ) Tj 5.4 0 Td 55.833333 Tz (phosphonic ) Tj 3.55 0 Td 49.166667 Tz (acids ) Tj 1.7 0 Td 57.291667 Tz (\(JGW-8\), ) Tj 33.571429 0 0 33.571429 0 2397.787383 Tm 15.4 0 Td 84.397163 Tz (R ) Tj 0.744681 0 Td 84.397163 Tz (= ) Tj 0.685106 0 Td 69.503546 Tz (C17H33 ) Tj 2.740426 0 Td 69.503546 Tz (O ) Tj 0.953191 0 Td 64.539007 Tz (C15H31, ) Tj 2.948936 0 Td 104.255319 Tz (X ) Tj 0.834043 0 Td 84.397163 Tz (= ) Tj 0.714894 0 Td 69.503546 Tz (H, ) Tj 1.042553 0 Td 57.919622 Tz (Cl, ) Tj 1.251064 0 Td 61.229314 Tz (Br, ) Tj 1.310638 0 Td 64.539007 Tz (or ) Tj 0.982979 0 Td 101.77305 Tz (OH ) Tj 31.428571 0 0 31.428571 0 2362 Tm 27.681818 0 Td 111.363636 Tz (O ) Tj 93.333333 0 0 93.333333 0 2278.027027 Tm 6.460714 0 Td 25 Tz (S ) Tj 3.042857 0 Td 69.642857 Tz (Xu ) Tj 0.975 0 Td 33.928571 Tz (R ) Tj 185.714286 0 0 185.714286 0 2267 Tm 3.295385 0 Td 175 Tz (y ) Tj 57.142857 0 0 57.142857 0 2206 Tm 9.7125 0 Td 84.583333 Tz (HO1V ) Tj 31.428571 0 0 31.428571 0 2184 Tm 21.190909 0 Td 111.363636 Tz (OH ) Tj 40 0 0 40 0 2126.568389 Tm 14.875 0 Td 56.944444 Tz (Darmstoff ) Tj 3.15 0 Td 51.190476 Tz (analog, ) Tj 2.35 0 Td 83.333333 Tz (R ) Tj 0.65 0 Td 70.833333 Tz (= ) Tj 0.6 0 Td 57.638889 Tz (C17H33 ) Tj 42.857143 0 0 42.857143 0 2084 Tm 18.106667 0 Td 68.703704 Tz (NH2 ) Tj 31.428571 0 0 31.428571 0 2604 Tm 18.104545 0 Td 111.363636 Tz (O ) Tj 52.857143 0 0 52.857143 0 2568 Tm 10.991892 0 Td 91.441441 Tz (V ) Tj 31.428571 0 0 31.428571 0 2529 Tm 18.454545 0 Td 90.151515 Tz (1 ) Tj 82.857143 0 0 82.857143 0 2510 Tm 7.313793 0 Td 70.402299 Tz (K ) Tj 31.428571 0 0 31.428571 0 2513 Tm 16.704545 0 Td 106.060606 Tz (HO ) Tj 31.428571 0 0 31.428571 0 2050 Tm 18.104545 0 Td 111.363636 Tz (O ) Tj 31.428571 0 0 31.428571 0 2059 Tm 24.818182 0 Td 68.939394 Tz (E ) Tj 54.761905 0 0 54.761905 0 2010.153846 Tm 10.609565 0 Td 88.26087 Tz (V ) Tj 1.04087 0 Td 65.434783 Tz (-O ) Tj 4.83913 0 Td 124.782609 Tz (N-R ) Tj 31.428571 0 0 31.428571 0 1982.5 Tm 18.390909 0 Td 100.757576 Tz (1 ) Tj 0.890909 0 Td 79.545455 Tz (P ) Tj 52.857143 0 0 52.857143 0 1956 Tm 9.913514 0 Td 71.471471 Tz (HO1 ) Tj 1.759459 0 Td 75.675676 Tz (V ) Tj 31.428571 0 0 31.428571 0 1930 Tm 20.204545 0 Td 111.363636 Tz (OH ) Tj 6.3 0 Td 111.363636 Tz (OH ) Tj 40 0 0 40 0 1880.237864 Tm 13.85 0 Td 54.545455 Tz (Sphingosine ) Tj 3.825 0 Td 51.041667 Tz (1-phosphate, ) Tj 3.9 0 Td 83.333333 Tz (R ) Tj 0.65 0 Td 70.833333 Tz (= ) Tj 0.6 0 Td 58.333333 Tz (C13H27 ) Tj 31.428571 0 0 31.428571 0 1843 Tm 19.027273 0 Td 111.363636 Tz (O ) Tj 61.428571 0 0 61.428571 0 1802 Tm 8.986047 0 Td 78.682171 Tz (HON ) Tj 31.428571 0 0 31.428571 0 1786 Tm 23.704545 0 Td 121.969697 Tz (Y ) Tj 28.928571 0 0 28.928571 0 1718.609375 Tm 21.846914 0 Td 120.987654 Tz (X ) Tj 4.701235 0 Td 28.806584 Tz (r ) Tj 3.249383 0 Td 120.987654 Tz (O ) Tj 4.079012 0 Td 97.942387 Tz (R ) Tj 96.190476 0 0 96.190476 0 1681.100877 Tm 6.840594 0 Td 159.405941 Tz (- ) Tj 1.268317 0 Td 28.069307 Tz ('',1. ) Tj 1.44505 0 Td 95.29703 Tz (r ) Tj 31.428571 0 0 31.428571 0 1618 Tm 29.272727 0 Td 111.363636 Tz (O ) Tj 40 0 0 40 0 1561.488636 Tm 12.025 0 Td 55.952381 Tz (2-Carba ) Tj 2.525 0 Td 48.611111 Tz (cyclic ) Tj 1.925 0 Td 51.736111 Tz (phosphatidic ) Tj 3.875 0 Td 47.5 Tz (acid, ) Tj 1.6 0 Td 95.833333 Tz (X ) Tj 0.725 0 Td 70.833333 Tz (= ) Tj 0.6 0 Td 58.333333 Tz (O, ) Tj 0.875 0 Td 91.666667 Tz (Y ) Tj 0.725 0 Td 70.833333 Tz (= ) Tj 0.575 0 Td 70.833333 Tz (CH2 ) Tj 40 0 0 40 0 1527.479245 Tm 12.025 0 Td 55.952381 Tz (3-Carba ) Tj 2.525 0 Td 48.611111 Tz (cyclic ) Tj 1.925 0 Td 51.736111 Tz (phosphatidic ) Tj 3.875 0 Td 47.5 Tz (acid, ) Tj 1.6 0 Td 95.833333 Tz (X ) Tj 0.725 0 Td 70.833333 Tz (= ) Tj 0.6 0 Td 60.416667 Tz (CH2, ) Tj 1.625 0 Td 95.833333 Tz (Y ) Tj 0.725 0 Td 70.833333 Tz (= ) Tj 0.575 0 Td 91.666667 Tz (O ) Tj 31.428571 0 0 31.428571 0 1487 Tm 25.263636 0 Td 111.363636 Tz (OH ) Tj 31.428571 0 0 31.428571 0 1445 Tm 17.118182 0 Td 111.363636 Tz (OH ) Tj 81.428571 0 0 81.428571 0 1387 Tm 5.710526 0 Td 79.824561 Tz (s/ ) Tj 48.571429 0 0 48.571429 0 1351 Tm 10.108824 0 Td 61.764706 Tz (W ) Tj 35 0 0 35 0 1321.021505 Tm 12.914286 0 Td 95.238095 Tz (HO ) Tj 8.085714 0 Td 84.126984 Tz (NH2 ) Tj 31.428571 0 0 31.428571 0 1254 Tm 34.522727 0 Td 90.151515 Tz (R ) Tj 40 0 0 40 0 1199.069565 Tm 14.8 0 Td 57.352941 Tz (FTY720-phosphate, ) Tj 6.075 0 Td 79.166667 Tz (R ) Tj 0.6 0 Td 75 Tz (= ) Tj 0.625 0 Td 61.666667 Tz (CsH17 ) Tj 31.428571 0 0 31.428571 0 1163 Tm 24.659091 0 Td 111.363636 Tz (OH ) Tj 31.428571 0 0 31.428571 0 1119.512195 Tm 18.104545 0 Td 111.363636 Tz (O ) Tj 10.309091 0 Td 106.060606 Tz (H ) Tj 38.571429 0 0 38.571429 0 1091.567164 Tm 15.062963 0 Td 116.666667 Tz (V ) Tj 8.011111 0 Td 99.382716 Tz (N ) Tj 3.059259 0 Td 73.45679 Tz (R ) Tj 31.428571 0 0 31.428571 0 1063 Tm 19.281818 0 Td 79.545455 Tz (P ) Tj 86.428571 0 0 86.428571 0 1025.070175 Tm 6.07438 0 Td 55.922865 Tz (HO1V ) Tj 4.894215 0 Td 106.060606 Tz (r ) Tj 31.428571 0 0 31.428571 0 1002 Tm 20.204545 0 Td 111.363636 Tz (OH ) Tj 9.990909 0 Td 111.363636 Tz (O ) Tj 32.857143 0 0 32.857143 0 796 Tm 18.321739 0 Td 96.376812 Tz (R ) Tj 40 0 0 40 0 737.181818 Tm 13.475 0 Td 55.555556 Tz (Phosphonates ) Tj 4.25 0 Td 57.575758 Tz (\(VPC8a202\), ) Tj 4.05 0 Td 79.166667 Tz (R ) Tj 0.65 0 Td 66.666667 Tz (= ) Tj 0.525 0 Td 64.583333 Tz (C5H31, ) Tj 41.428571 0 0 41.428571 0 700.680525 Tm 12.768966 0 Td 80.45977 Tz (R ) Tj 0.844828 0 Td 64.367816 Tz (= ) Tj 0.531034 0 Td 49.16986 Tz (aromatic, ) Tj 2.8 0 Td 49.08046 Tz (heteroaromatic, ) Tj 4.610345 0 Td 51.494253 Tz (cyclohexyl ) Tj 51.428571 0 0 51.428571 0 593.667093 Tm 7.097222 0 Td 58.981481 Tz (While ) Tj 1.983333 0 Td 64.814815 Tz (many ) Tj 1.75 0 Td 59.953704 Tz (of ) Tj 0.797222 0 Td 50.555556 Tz (these ) Tj 1.711111 0 Td 44.074074 Tz (lipid ) Tj 1.477778 0 Td 53.240741 Tz (analogs ) Tj 2.430556 0 Td 49.691358 Tz (are ) Tj 1.05 0 Td 51.311728 Tz (potent ) Tj 2.002778 0 Td 77.777778 Tz (ATX ) Tj 1.594444 0 Td 53.472222 Tz (inhibi ) Tj 51.428571 0 0 51.428571 0 549.396887 Tm 6.338889 0 Td 42.777778 Tz (tors, ) Tj 1.594444 0 Td 50.231481 Tz (they ) Tj 1.497222 0 Td 51.041667 Tz (lack ) Tj 1.516667 0 Td 64.814815 Tz (many ) Tj 1.827778 0 Td 46.234568 Tz (characteristics ) Tj 4.452778 0 Td 53.472222 Tz (seen ) Tj 1.575 0 Td 45.37037 Tz (in ) Tj 0.816667 0 Td 73.45679 Tz (90% ) Tj 1.633333 0 Td 56.712963 Tz (of ) Tj 0.855556 0 Td 48.070988 Tz (orally ) Tj 51.428571 0 0 51.428571 0 507.945083 Tm 6.338889 0 Td 49.151235 Tz (bioavailable ) Tj 3.927778 0 Td 49.691358 Tz (drugs, ) Tj 2.158333 0 Td 59.41358 Tz (and ) Tj 1.419444 0 Td 46.720679 Tz (collectively ) Tj 3.733333 0 Td 51.041667 Tz (they ) Tj 1.652778 0 Td 50.231481 Tz (lack ) Tj 1.575 0 Td 45.959596 Tz (significant ) Tj 51.428571 0 0 51.428571 0 462.912409 Tm 6.377778 0 Td 45.37037 Tz (structural ) Tj 2.936111 0 Td 43.425926 Tz (diversity. ) Tj 51.428571 0 0 51.428571 0 421.634543 Tm 7.116667 0 Td 44.965278 Tz (Finally, ) Tj 2.333333 0 Td 50.771605 Tz (the ) Tj 1.05 0 Td 46.018519 Tz (third ) Tj 1.536111 0 Td 51.446759 Tz (category ) Tj 2.644444 0 Td 58.333333 Tz (of ) Tj 0.777778 0 Td 50.636574 Tz (reported ) Tj 2.547222 0 Td 78.858025 Tz (ATX ) Tj 1.575 0 Td 46.342593 Tz (inhibitors ) Tj 2.955556 0 Td 71.296296 Tz (con ) Tj 51.428571 0 0 51.428571 0 379.148194 Tm 6.377778 0 Td 40.833333 Tz (sists ) Tj 1.497222 0 Td 59.953704 Tz (of ) Tj 0.913889 0 Td 46.666667 Tz (non-lipid, ) Tj 3.072222 0 Td 51.851852 Tz (small ) Tj 1.886111 0 Td 53.652263 Tz (molecules ) Tj 3.169444 0 Td 45.37037 Tz (that ) Tj 1.361111 0 Td 46.450617 Tz (collectively ) Tj 3.597222 0 Td 55.092593 Tz (extend ) Tj 51.428571 0 0 51.428571 0 340.828709 Tm 6.377778 0 Td 45.37037 Tz (structural ) Tj 2.975 0 Td 46.090535 Tz (diversity ) Tj 2.702778 0 Td 60.493827 Tz (and ) Tj 1.302778 0 Td 46.990741 Tz (in ) Tj 0.777778 0 Td 51.388889 Tz (general ) Tj 2.372222 0 Td 52.314815 Tz (possess ) Tj 2.411111 0 Td 54.444444 Tz (physicochemical ) Tj 51.428571 0 0 51.428571 0 294.942138 Tm 6.358333 0 Td 46.234568 Tz (characteristics ) Tj 4.511111 0 Td 61.574074 Tz (more ) Tj 1.788889 0 Td 49.074074 Tz (closely ) Tj 2.45 0 Td 46.759259 Tz (related ) Tj 2.275 0 Td 45.37037 Tz (to ) Tj 0.894444 0 Td 46.990741 Tz (orally ) Tj 2.002778 0 Td 49.421296 Tz (bioavailable ) Tj 51.428571 0 0 51.428571 0 253.405797 Tm 6.358333 0 Td 49.151235 Tz (drugs. ) Tj 2.002778 0 Td 63.734568 Tz (The ) Tj 1.4 0 Td 58.333333 Tz (most ) Tj 1.613889 0 Td 47.43266 Tz (efficacious ) Tj 3.363889 0 Td 46.990741 Tz (structures ) Tj 3.033333 0 Td 51.203704 Tz (previously ) Tj 3.325 0 Td 46.018519 Tz (identified ) Tj 51.428571 0 0 51.428571 0 211.776699 Tm 6.358333 0 Td 49.691358 Tz (are ) Tj 1.030556 0 Td 62.222222 Tz (shown ) Tj 1.963889 0 Td 45.37037 Tz (in ) Tj 0.680556 0 Td 55.740741 Tz (group ) Tj 1.827778 0 Td 52.391975 Tz (Figure ) Tj 1.983333 0 Td 53.472222 Tz (A, ) Tj 0.777778 0 Td 51.851852 Tz (below. ) Tj 2.061111 0 Td 71.296296 Tz (H2L ) Tj 1.419444 0 Td 59.722222 Tz (7905958 ) Tj 2.644444 0 Td 47.530864 Tz (\(1\) ) Tj 0.952778 0 Td 61.574074 Tz (was ) Tj 1.244444 0 Td 49.691358 Tz (the ) Tj 51.428571 0 0 51.428571 0 170.426634 Tm 6.358333 0 Td 59.143519 Tz (most ) Tj 1.652778 0 Td 47.138047 Tz (efficacious ) Tj 3.363889 0 Td 64.00463 Tz (compound ) Tj 3.286111 0 Td 58.333333 Tz (from ) Tj 1.633333 0 Td 46.180556 Tz (that ) Tj 1.361111 0 Td 39.351852 Tz (initial ) Tj 1.925 0 Td 47.530864 Tz (single ) Tj 1.944444 0 Td 63.734568 Tz (concen ) Tj 30 0 0 30 0 2547 Tm 41.666667 0 Td 75 Tz (10 ) Tj 30 0 0 30 0 2339 Tm 41.666667 0 Td 72.222222 Tz (15 ) Tj 30 0 0 30 0 1923 Tm 41.6 0 Td 77.777778 Tz (25 ) Tj 30 0 0 30 0 1716 Tm 41.6 0 Td 80.555556 Tz (30 ) Tj 30 0 0 30 0 1507 Tm 41.6 0 Td 77.777778 Tz (35 ) Tj 30 0 0 30 0 1299 Tm 41.566667 0 Td 83.333333 Tz (40 ) Tj 30 0 0 30 0 1091 Tm 41.566667 0 Td 80.555556 Tz (45 ) Tj 30 0 0 30 0 883 Tm 41.6 0 Td 80.555556 Tz (50 ) Tj 30 0 0 30 0 675 Tm 41.6 0 Td 77.777778 Tz (55 ) Tj 30 0 0 30 0 467 Tm 41.633333 0 Td 77.777778 Tz (60 ) Tj 30 0 0 30 0 259 Tm 41.633333 0 Td 75 Tz (65 ) Tj 51.428571 0 0 51.428571 0 2969 Tm 33.775 0 Td 77.777778 Tz (4 ) Tj 51.428571 0 0 51.428571 0 2915.343226 Tm 25.277778 0 Td 45.37037 Tz (tration ) Tj 2.158333 0 Td 51.311728 Tz (screen ) Tj 2.1 0 Td 43.209877 Tz (\(at ) Tj 1.069444 0 Td 58.333333 Tz (10 ) Tj 0.952778 0 Td 81.018519 Tz (uM ) Tj 1.225 0 Td 64.00463 Tz (compound ) Tj 3.363889 0 Td 38.888889 Tz (1 ) Tj 0.563889 0 Td 44.722222 Tz (fully ) Tj 1.613889 0 Td 47.890947 Tz (inhibited ) Tj 2.8 0 Td 90.740741 Tz (ATX ) Tj 51.428571 0 0 51.428571 0 2874.491591 Tm 25.297222 0 Td 51.131687 Tz (catalyzed ) Tj 3.072222 0 Td 50.231481 Tz (hydrolysis ) Tj 3.344444 0 Td 59.953704 Tz (of ) Tj 0.972222 0 Td 38.888889 Tz (1 ) Tj 0.7 0 Td 77.777778 Tz (uM ) Tj 1.302778 0 Td 49.151235 Tz (FS-3\). ) Tj 2.177778 0 Td 49.331276 Tz (Recently, ) Tj 2.955556 0 Td 48.935185 Tz (additional ) Tj 51.428571 0 0 51.428571 0 2828.079602 Tm 25.316667 0 Td 53.240741 Tz (small-molecule ) Tj 4.686111 0 Td 46.342593 Tz (inhibitors ) Tj 3.013889 0 Td 59.953704 Tz (of ) Tj 0.797222 0 Td 78.858025 Tz (ATX ) Tj 1.672222 0 Td 52.932099 Tz (\(group ) Tj 2.158333 0 Td 51.388889 Tz (Figures ) Tj 2.45 0 Td 68.055556 Tz (B ) Tj 0.661111 0 Td 58.333333 Tz (and ) Tj 1.283333 0 Td 59.953704 Tz (C\) ) Tj 51.428571 0 0 51.428571 0 2783.313131 Tm 25.277778 0 Td 59.953704 Tz (were ) Tj 1.711111 0 Td 45.694444 Tz (identified ) Tj 2.955556 0 Td 51.851852 Tz (as ) Tj 0.894444 0 Td 46.8107 Tz (potential ) Tj 2.780556 0 Td 51.851852 Tz (as ) Tj 0.913889 0 Td 49.583333 Tz (metastasis ) Tj 3.208333 0 Td 51.041667 Tz (blockers ) Tj 2.702778 0 Td 51.851852 Tz (as ) Tj 0.894444 0 Td 46.666667 Tz (well. ) Tj 51.428571 0 0 51.428571 0 2742.68021 Tm 25.297222 0 Td 68.055556 Tz (One ) Tj 1.516667 0 Td 60.493827 Tz (compound, ) Tj 3.597222 0 Td 77.777778 Tz (NSC ) Tj 1.730556 0 Td 55.092593 Tz (48300, ) Tj 2.313889 0 Td 45.37037 Tz (in ) Tj 0.875 0 Td 56.388889 Tz (group ) Tj 2.061111 0 Td 51.851852 Tz (Figure ) Tj 2.177778 0 Td 55.092593 Tz (C, ) Tj 1.011111 0 Td 61.033951 Tz (showed ) Tj 51.428571 0 0 51.428571 0 2696.479388 Tm 25.297222 0 Td 46.254209 Tz (essentially ) Tj 3.247222 0 Td 67.24537 Tz (100% ) Tj 1.75 0 Td 46.666667 Tz (inhibition ) Tj 2.955556 0 Td 53.472222 Tz (of ) Tj 0.719444 0 Td 62.789352 Tz (melanoma ) Tj 3.130556 0 Td 49.583333 Tz (metastasis ) Tj 3.091667 0 Td 43.75 Tz (at ) Tj 0.680556 0 Td 62.87037 Tz (micro ) Tj 51.428571 0 0 51.428571 0 2654.162791 Tm 25.297222 0 Td 57.685185 Tz (molar ) Tj 2.119444 0 Td 48.611111 Tz (concentrations. ) Tj 4.783333 0 Td 56.30787 Tz (Although ) Tj 3.130556 0 Td 42.939815 Tz (this ) Tj 1.438889 0 Td 60.133745 Tz (compound, ) Tj 3.636111 0 Td 59.41358 Tz (and ) Tj 1.458333 0 Td 49.691358 Tz (the ) Tj 51.428571 0 0 51.428571 0 2612.018824 Tm 25.297222 0 Td 56.388889 Tz (group ) Tj 1.886111 0 Td 56.712963 Tz (of ) Tj 0.758333 0 Td 61.934156 Tz (compounds ) Tj 3.519444 0 Td 49.074074 Tz (similar ) Tj 2.177778 0 Td 46.180556 Tz (thereto, ) Tj 2.372222 0 Td 50.411523 Tz (exhibited ) Tj 2.858333 0 Td 49.494949 Tz (acceptable, ) Tj 3.441667 0 Td 45.37037 Tz (if ) Tj 48.571429 0 0 48.571429 0 2566 Tm 26.826471 0 Td 52.614379 Tz (not ) Tj 1.132353 0 Td 49.183007 Tz (effective ) Tj 2.820588 0 Td 53.376906 Tz (autotaxin ) Tj 3.088235 0 Td 48.039216 Tz (inhibition, ) Tj 3.376471 0 Td 36.029412 Tz (it ) Tj 0.617647 0 Td 41.176471 Tz (is ) Tj 0.741176 0 Td 53.75817 Tz (not ) Tj 1.132353 0 Td 50.784314 Tz (clear ) Tj 1.688235 0 Td 46.323529 Tz (if ) Tj 0.658824 0 Td 58.333333 Tz (such ) Tj 1.605882 0 Td 88.071895 Tz (com ) Tj 51.428571 0 0 51.428571 0 2521.714286 Tm 25.277778 0 Td 58.333333 Tz (pounds ) Tj 2.275 0 Td 50.771605 Tz (are ) Tj 1.088889 0 Td 46.8107 Tz (selective ) Tj 2.722222 0 Td 45.37037 Tz (to ) Tj 0.719444 0 Td 76.697531 Tz (ATX ) Tj 1.575 0 Td 55.555556 Tz (\(NPP2\). ) Tj 30 0 0 30 0 2400 Tm 43.333333 0 Td 127.777778 Tz (A ) Tj 31.428571 0 0 31.428571 0 2324 Tm 64.940909 0 Td 88.383838 Tz (H2L ) Tj 1.877273 0 Td 66.950758 Tz (52.10574 ) Tj 31.428571 0 0 31.428571 0 2154 Tm 41.65 0 Td 106.060606 Tz (HO ) Tj 31.428571 0 0 31.428571 0 2126 Tm 63.859091 0 Td 121.969697 Tz (N ) Tj 31.428571 0 0 31.428571 0 2068 Tm 50.113636 0 Td 111.363636 Tz (O ) Tj 31.428571 0 0 31.428571 0 2030 Tm 63.731818 0 Td 111.363636 Tz (O ) Tj 31.428571 0 0 31.428571 0 1982 Tm 64.909091 0 Td 90.151515 Tz (H2L ) Tj 1.909091 0 Td 75.757576 Tz (7839888 ) Tj 141.428571 0 0 141.428571 0 1579 Tm 13.215152 0 Td 78.367003 Tz (NY ) Tj 31.428571 0 0 31.428571 0 1555 Tm 60.740909 0 Td 106.060606 Tz (HN ) Tj 4.231818 0 Td 111.363636 Tz (O ) Tj 31.428571 0 0 31.428571 0 1321 Tm 63.127273 0 Td 111.363636 Tz (O ) Tj 31.428571 0 0 31.428571 0 1270 Tm 64.940909 0 Td 88.383838 Tz (H2L ) Tj 1.877273 0 Td 75 Tz (5761473 ) Tj 31.428571 0 0 31.428571 0 1199.666667 Tm 48.809091 0 Td 111.363636 Tz (O ) Tj 6.490909 0 Td 111.363636 Tz (O ) Tj 6.490909 0 Td 111.363636 Tz (O ) Tj 230 0 0 230 0 1046 Tm 6.978261 0 Td 85.748792 Tz (CO: ) Tj 31.428571 0 0 31.428571 0 1025 Tm 48.809091 0 Td 111.363636 Tz (O ) Tj 12.981818 0 Td 111.363636 Tz (O ) Tj 31.428571 0 0 31.428571 0 935 Tm 41.65 0 Td 106.060606 Tz (HO ) Tj 26.695455 0 Td 114.015152 Tz (OH ) Tj 31.428571 0 0 31.428571 0 892 Tm 44.672727 0 Td 111.363636 Tz (O ) Tj 21.286364 0 Td 111.363636 Tz (O ) Tj 40 0 0 40 0 840 Tm 49.95 0 Td 72.222222 Tz (H2L ) Tj 1.525 0 Td 59.52381 Tz (7905958 ) Tj 2.7 0 Td 45.833333 Tz (\(1\) ) Tj 138.571429 0 0 138.571429 0 445 Tm 13.595876 0 Td 40.893471 Tz (N. ) Tj 31.428571 0 0 31.428571 0 420 Tm 68.409091 0 Td 111.363636 Tz (C ) Tj 31.428571 0 0 31.428571 0 220 Tm 64.75 0 Td 111.363636 Tz (C ) Tj 1.428571 0 0 1.428571 0 812 Tm 921.2 0 Td 116.666667 Tz ( ) Tj ET Q endstream endobj 284 0 obj << /Length 1 >> stream q endstream endobj 285 0 obj << /Length 12015 >> stream Q q 0.24 0 0 0.24 0 0 cm BT /F1 1 Tf 3 Tr 62.857143 0 0 62.857143 0 3023 Tm 17.325 0 Td 83.522727 Tz (US ) Tj 1.240909 0 Td 57.154882 Tz (8,497,371 ) Tj 3.388636 0 Td 74.242424 Tz (B2 ) Tj 40 0 0 40 0 2913 Tm 17.475 0 Td 67.083333 Tz (-continued ) Tj 31.428571 0 0 31.428571 0 2868 Tm 33.918182 0 Td 91.919192 Tz (H2L ) Tj 1.877273 0 Td 76.515152 Tz (5564949 ) Tj 31.428571 0 0 31.428571 0 2799.5 Tm 17.436364 0 Td 111.363636 Tz (O ) Tj 7.286364 0 Td 111.363636 Tz (O ) Tj 31.428571 0 0 31.428571 0 2724 Tm 15.304545 0 Td 106.060606 Tz (HN ) Tj 31.428571 0 0 31.428571 0 2696 Tm 24.881818 0 Td 121.969697 Tz (N ) Tj 7.222727 0 Td 121.969697 Tz (N ) Tj 35.714286 0 0 35.714286 0 2669 Tm 28.644 0 Td 88.666667 Tz (w ) Tj 31.428571 0 0 31.428571 0 2646 Tm 32.995455 0 Td 121.969697 Tz (N ) Tj 31.428571 0 0 31.428571 0 2588.196721 Tm 10.563636 0 Td 106.060606 Tz (HO ) Tj 14.159091 0 Td 111.363636 Tz (O ) Tj 31.428571 0 0 31.428571 0 2497 Tm 12.727273 0 Td 111.363636 Tz (O ) Tj 31.428571 0 0 31.428571 0 2440 Tm 33.95 0 Td 90.151515 Tz (H2L ) Tj 1.877273 0 Td 65.625 Tz (7921.385 ) Tj 130 0 0 130 0 2302 Tm 5.323077 0 Td 53.846154 Tz (u ) Tj 31.428571 0 0 31.428571 0 2283 Tm 21.127273 0 Td 121.969697 Tz (N ) Tj 31.428571 0 0 31.428571 0 2241 Tm 28.381818 0 Td 106.060606 Tz (H ) Tj 72.142857 0 0 72.142857 0 2204.429825 Tm 8.732673 0 Td 70.077008 Tz (als ) Tj 3.590099 0 Td 53.135314 Tz (N ) Tj 77.857143 0 0 77.857143 0 2152.666667 Tm 7.809174 0 Td 49.235474 Tz (N ) Tj 1.489908 0 Td 107.033639 Tz (s^ ) Tj 31.428571 0 0 31.428571 0 2121 Tm 26.504545 0 Td 111.363636 Tz (O ) Tj 10.754545 0 Td 111.363636 Tz (OH ) Tj 31.428571 0 0 31.428571 0 2023 Tm 35.477273 0 Td 111.363636 Tz (O ) Tj 31.428571 0 0 31.428571 0 1974 Tm 10.5 0 Td 90.151515 Tz (B ) Tj 31.428571 0 0 31.428571 0 1901 Tm 19.504545 0 Td 111.363636 Tz (OH ) Tj 9.831818 0 Td 111.363636 Tz (OH ) Tj 31.428571 0 0 31.428571 0 1834 Tm 15.4 0 Td 111.363636 Tz (C ) Tj 17.627273 0 Td 111.363636 Tz (C ) Tj 31.428571 0 0 31.428571 0 1701 Tm 23.195455 0 Td 111.363636 Tz (C ) Tj 2.036364 0 Td 74.242424 Tz (Cl ) Tj 32.857143 0 0 32.857143 0 1633 Tm 18.686957 0 Td 101.449275 Tz (C ) Tj 9.404348 0 Td 101.449275 Tz (C ) Tj 40 0 0 40 0 1581 Tm 16.8 0 Td 57.222222 Tz (Hexachlorophene ) Tj 31.428571 0 0 31.428571 0 1405 Tm 27.904545 0 Td 111.363636 Tz (COOH ) Tj 31.428571 0 0 31.428571 0 1338 Tm 16.481818 0 Td 74.242424 Tz (Br ) Tj 15.177273 0 Td 76.893939 Tz (Br ) Tj 48.571429 0 0 48.571429 0 1308 Tm 14.823529 0 Td 87.5 Tz (21 ) Tj 31.428571 0 0 31.428571 0 1205 Tm 16.863636 0 Td 111.363636 Tz (O ) Tj 7.35 0 Td 111.363636 Tz (O ) Tj 7.35 0 Td 111.363636 Tz (OH ) Tj 40 0 0 40 0 1138 Tm 21.9 0 Td 75 Tz (Hg ) Tj 31.428571 0 0 31.428571 0 1080 Tm 22.559091 0 Td 78.367003 Tz (Merbromin ) Tj 31.428571 0 0 31.428571 0 974 Tm 20.745455 0 Td 111.363636 Tz (OH ) Tj 7.35 0 Td 111.363636 Tz (OH ) Tj 34.285714 0 0 34.285714 0 905 Tm 15.254167 0 Td 75.347222 Tz (Cl ) Tj 7.204167 0 Td 48.611111 Tz (S. ) Tj 6.679167 0 Td 65.625 Tz (Cl ) Tj 31.428571 0 0 31.428571 0 707 Tm 20.777273 0 Td 111.363636 Tz (C ) Tj 7.35 0 Td 111.363636 Tz (C ) Tj 31.428571 0 0 31.428571 0 655 Tm 22.940909 0 Td 64.225589 Tz (Bithionol ) Tj 31.428571 0 0 31.428571 0 549 Tm 19.472727 0 Td 111.363636 Tz (OH ) Tj 7.35 0 Td 111.363636 Tz (OH ) Tj 31.428571 0 0 31.428571 0 482 Tm 30.513636 0 Td 111.363636 Tz (C ) Tj 31.428571 0 0 31.428571 0 349 Tm 22.527273 0 Td 106.060606 Tz (HO ) Tj 31.428571 0 0 31.428571 0 282 Tm 19.504545 0 Td 111.363636 Tz (C ) Tj 41.428571 0 0 41.428571 0 227 Tm 13.831034 0 Td 49.373041 Tz (2,2'-methylenebis\(4-chlorophenol\) ) Tj 30 0 0 30 0 2755 Tm 41.833333 0 Td 72.222222 Tz (5 ) Tj 30 0 0 30 0 2547 Tm 41.666667 0 Td 75 Tz (10 ) Tj 30 0 0 30 0 2339 Tm 41.666667 0 Td 72.222222 Tz (15 ) Tj 30 0 0 30 0 1923 Tm 41.6 0 Td 77.777778 Tz (25 ) Tj 30 0 0 30 0 1716 Tm 41.6 0 Td 80.555556 Tz (30 ) Tj 30 0 0 30 0 1507 Tm 41.6 0 Td 77.777778 Tz (35 ) Tj 30 0 0 30 0 1299 Tm 41.566667 0 Td 83.333333 Tz (40 ) Tj 30 0 0 30 0 1091 Tm 41.566667 0 Td 80.555556 Tz (45 ) Tj 30 0 0 30 0 883 Tm 41.6 0 Td 80.555556 Tz (50 ) Tj 30 0 0 30 0 675 Tm 41.6 0 Td 77.777778 Tz (55 ) Tj 30 0 0 30 0 467 Tm 41.633333 0 Td 77.777778 Tz (60 ) Tj 30 0 0 30 0 259 Tm 41.633333 0 Td 75 Tz (65 ) Tj 40 0 0 40 0 2913 Tm 41.825 0 Td 66.666667 Tz (-continued ) Tj 31.428571 0 0 31.428571 0 2764 Tm 58.990909 0 Td 111.363636 Tz (COOH ) Tj 31.428571 0 0 31.428571 0 2698 Tm 47.568182 0 Td 74.242424 Tz (Br ) Tj 15.209091 0 Td 74.242424 Tz (Br ) Tj 48.571429 0 0 48.571429 0 2668 Tm 34.938235 0 Td 87.5 Tz (21 ) Tj 31.428571 0 0 31.428571 0 2564 Tm 47.345455 0 Td 106.060606 Tz (HO ) Tj 7.954545 0 Td 111.363636 Tz (O ) Tj 7.35 0 Td 111.363636 Tz (OH ) Tj 31.428571 0 0 31.428571 0 2498 Tm 51.736364 0 Td 76.893939 Tz (Br ) Tj 7.35 0 Td 76.893939 Tz (Br ) Tj 31.428571 0 0 31.428571 0 2439 Tm 54.218182 0 Td 65.757576 Tz (Eosin ) Tj 2.227273 0 Td 121.969697 Tz (Y ) Tj 31.428571 0 0 31.428571 0 2385 Tm 65.863636 0 Td 86.616162 Tz (RJC ) Tj 1.813636 0 Td 77.424242 Tz (03297 ) Tj 31.428571 0 0 31.428571 0 2357 Tm 53.390909 0 Td 74.242424 Tz (S ) Tj 31.428571 0 0 31.428571 0 2224 Tm 53.295455 0 Td 111.363636 Tz (O ) Tj 31.428571 0 0 31.428571 0 2194 Tm 41.395455 0 Td 100.757576 Tz (C ) Tj 31.428571 0 0 31.428571 0 2127 Tm 65.927273 0 Td 84.848485 Tz (NSC48300 ) Tj 59.285714 0 0 59.285714 0 2014.84 Tm 23.985542 0 Td 92.771084 Tz (V ) Tj 8.737349 0 Td 59.036145 Tz (OH ) Tj 30 0 0 30 0 1974 Tm 48.133333 0 Td 91.666667 Tz (As ) Tj 15.466667 0 Td 86.111111 Tz (As ) Tj 54.285714 0 0 54.285714 0 1937.563725 Tm 25.2 0 Td 88.267544 Tz (HO1V ) Tj 9.560526 0 Td 73.684211 Tz (M ) Tj 0.957895 0 Td 66.520468 Tz (YOH ) Tj 31.428571 0 0 31.428571 0 1917 Tm 47.027273 0 Td 111.363636 Tz (OH ) Tj 12.568182 0 Td 111.363636 Tz (O ) Tj 31.428571 0 0 31.428571 0 1877 Tm 65.863636 0 Td 86.174242 Tz (NSC13792 ) Tj 91.428571 0 0 91.428571 0 1820 Tm 20.890625 0 Td 38.28125 Tz (pi ) Tj 171.428571 0 0 171.428571 0 1733 Tm 7.805 0 Td 41.805556 Tz (to--\( ) Tj 1.6275 0 Td 44.398148 Tz (\)-\( ) Tj 1.195833 0 Td 28.194444 Tz (\) ) Tj 0.670833 0 Td 31.759259 Tz (-on ) Tj 31.428571 0 0 31.428571 0 1715 Tm 45.372727 0 Td 111.363636 Tz (OH ) Tj 15.368182 0 Td 111.363636 Tz (O ) Tj 31.428571 0 0 31.428571 0 1678 Tm 65.927273 0 Td 84.848485 Tz (NSC6OO16 ) Tj 120 0 0 120 0 1577.586207 Tm 11.741667 0 Td 29.166667 Tz (O ) Tj 0.925 0 Td 52.777778 Tz (\( ) Tj 0.775 0 Td 54.166667 Tz (\) ) Tj 0.891667 0 Td 47.222222 Tz (\( ) Tj 0.858333 0 Td 40.277778 Tz (\) ) Tj 0.991667 0 Td 29.166667 Tz (OH ) Tj 31.428571 0 0 31.428571 0 1534 Tm 44.227273 0 Td 106.060606 Tz (HO ) Tj 17.563636 0 Td 111.363636 Tz (O ) Tj 31.428571 0 0 31.428571 0 1497 Tm 65.927273 0 Td 84.848485 Tz (NSC86629 ) Tj 270 0 0 270 0 1302 Tm 5.548148 0 Td 154.012346 Tz (CO ) Tj 31.428571 0 0 31.428571 0 1277 Tm 45.627273 0 Td 111.363636 Tz (OH ) Tj 14.7 0 Td 111.363636 Tz (O ) Tj 31.428571 0 0 31.428571 0 1238 Tm 65.927273 0 Td 83.522727 Tz (NSC10881 ) Tj 140 0 0 140 0 1100.467662 Tm 11.3 0 Td 88.690476 Tz (Ol ) Tj 1.35 0 Td 30.952381 Tz (pH ) Tj 78.571429 0 0 78.571429 0 1052 Tm 21.98 0 Td 152.727273 Tz (2 ) Tj 45.714286 0 0 45.714286 0 1048 Tm 37.8875 0 Td 72.916667 Tz (W ) Tj 1.159375 0 Td 72.916667 Tz (YOH ) Tj 31.428571 0 0 31.428571 0 1028 Tm 54.504545 0 Td 111.363636 Tz (O ) Tj 31.428571 0 0 31.428571 0 992 Tm 65.895455 0 Td 84.848485 Tz (NSC78785 ) Tj 226.428571 0 0 226.428571 0 786.275449 Tm 6.32429 0 Td 63.301788 Tz (- ) Tj 1.885804 0 Td 59.621451 Tz (- ) Tj 31.428571 0 0 31.428571 0 742 Tm 49.413636 0 Td 111.363636 Tz (O ) Tj 7.859091 0 Td 106.060606 Tz (HO ) Tj 51.428571 0 0 51.428571 0 633.483627 Tm 26.036111 0 Td 52.662037 Tz (Furthermore, ) Tj 4.025 0 Td 49.691358 Tz (the ) Tj 1.088889 0 Td 51.446759 Tz (previous ) Tj 2.683333 0 Td 76.697531 Tz (ATX ) Tj 1.594444 0 Td 47.314815 Tz (inhibiting ) Tj 3.033333 0 Td 61.934156 Tz (compounds ) Tj 3.577778 0 Td 39.969136 Tz (all ) Tj 51.428571 0 0 51.428571 0 587.765068 Tm 25.297222 0 Td 50.05144 Tz (exhibited ) Tj 2.994444 0 Td 46.296296 Tz (certain ) Tj 2.216667 0 Td 57.253086 Tz (drawbacks ) Tj 3.383333 0 Td 45.37037 Tz (in ) Tj 0.836111 0 Td 48.287037 Tz (largescale ) Tj 3.130556 0 Td 47.530864 Tz (potential ) Tj 2.838889 0 Td 49.074074 Tz (utiliza ) Tj 51.428571 0 0 51.428571 0 543.596577 Tm 25.277778 0 Td 43.425926 Tz (tion. ) Tj 1.516667 0 Td 56.17284 Tz (For ) Tj 1.186111 0 Td 46.8107 Tz (instance, ) Tj 2.702778 0 Td 49.421296 Tz (past ) Tj 1.341667 0 Td 63.194444 Tz (work ) Tj 1.672222 0 Td 43.75 Tz (at ) Tj 0.661111 0 Td 77.777778 Tz (ATX ) Tj 1.594444 0 Td 46.666667 Tz (inhibition ) Tj 2.975 0 Td 54.012346 Tz (has ) Tj 1.147222 0 Td 49.331276 Tz (included, ) Tj 51.428571 0 0 51.428571 0 504.10989 Tm 25.297222 0 Td 50.231481 Tz (as ) Tj 0.875 0 Td 52.5 Tz (noted ) Tj 1.788889 0 Td 52.932099 Tz (above, ) Tj 2.177778 0 Td 45.910494 Tz (L-histidine. ) Tj 3.597222 0 Td 50 Tz (Unfortunately, ) Tj 4.472222 0 Td 50.87963 Tz (millimolar ) Tj 3.266667 0 Td 71.296296 Tz (con ) Tj 51.428571 0 0 51.428571 0 463.893204 Tm 25.297222 0 Td 48.316498 Tz (centrations ) Tj 3.363889 0 Td 59.953704 Tz (were ) Tj 1.594444 0 Td 50.636574 Tz (required ) Tj 2.605556 0 Td 49.691358 Tz (for ) Tj 1.011111 0 Td 58.333333 Tz (any ) Tj 1.244444 0 Td 43.930041 Tz (efficacy, ) Tj 2.586111 0 Td 51.041667 Tz (and, ) Tj 1.438889 0 Td 61.574074 Tz (more ) Tj 1.672222 0 Td 64.814815 Tz (impor ) Tj 51.428571 0 0 51.428571 0 419.934673 Tm 25.277778 0 Td 43.055556 Tz (tantly, ) Tj 2.080556 0 Td 49.421296 Tz (zinc ) Tj 1.477778 0 Td 45.833333 Tz (sulfate ) Tj 2.216667 0 Td 45.775463 Tz (reversal ) Tj 2.488889 0 Td 59.953704 Tz (of ) Tj 0.855556 0 Td 43.75 Tz (this ) Tj 1.302778 0 Td 46.450617 Tz (effect ) Tj 1.905556 0 Td 44.290123 Tz (\(in ) Tj 1.069444 0 Td 52.849003 Tz (submillimolar ) Tj 51.428571 0 0 51.428571 0 378.415162 Tm 25.297222 0 Td 49.691358 Tz (concentrations\) ) Tj 4.744444 0 Td 52.932099 Tz (suggested ) Tj 3.072222 0 Td 58.333333 Tz (an ) Tj 0.972222 0 Td 46.666667 Tz (inhibition ) Tj 3.091667 0 Td 60.493827 Tz (mechanism ) Tj 3.519444 0 Td 57.253086 Tz (involv ) Tj 51.428571 0 0 51.428571 0 336.501333 Tm 25.297222 0 Td 50.771605 Tz (ing ) Tj 1.244444 0 Td 47.138047 Tz (interaction ) Tj 3.422222 0 Td 53.472222 Tz (with ) Tj 1.594444 0 Td 50.771605 Tz (the ) Tj 1.225 0 Td 59.41358 Tz (two ) Tj 1.419444 0 Td 48.611111 Tz (native ) Tj 2.041667 0 Td 48.070988 Tz (active ) Tj 2.041667 0 Td 42.12963 Tz (site ) Tj 1.341667 0 Td 53.148148 Tz (metal ) Tj 1.925 0 Td 50.231481 Tz (ions ) Tj 51.428571 0 0 51.428571 0 295.313131 Tm 25.277778 0 Td 46.585648 Tz (thereof. ) Tj 2.566667 0 Td 56.388889 Tz (Other ) Tj 1.944444 0 Td 46.8107 Tz (potential ) Tj 2.838889 0 Td 77.777778 Tz (ATX ) Tj 1.711111 0 Td 46.018519 Tz (inhibitors ) Tj 3.052778 0 Td 57.523148 Tz (have ) Tj 1.691667 0 Td 51.851852 Tz (included ) Tj 2.780556 0 Td 50.771605 Tz (the ) Tj 51.428571 0 0 51.428571 0 258.225319 Tm 25.297222 0 Td 51.851852 Tz (products ) Tj 2.605556 0 Td 56.712963 Tz (of ) Tj 0.758333 0 Td 55.840456 Tz (ATX-catalyzed ) Tj 4.452778 0 Td 50.555556 Tz (hydrolysis ) Tj 3.15 0 Td 56.712963 Tz (of ) Tj 0.758333 0 Td 72.376543 Tz (LPC ) Tj 1.419444 0 Td 58.333333 Tz (and ) Tj 1.166667 0 Td 52.5 Tz (sphingosyl ) Tj 51.428571 0 0 51.428571 0 215.474576 Tm 25.297222 0 Td 53.186275 Tz (phosphorylcholine ) Tj 5.619444 0 Td 54.552469 Tz (\(SPC\), ) Tj 2.197222 0 Td 60.763889 Tz (LPA, ) Tj 1.652778 0 Td 59.41358 Tz (and ) Tj 1.263889 0 Td 65.895062 Tz (S1P ) Tj 1.516667 0 Td 45.619658 Tz (respectively. ) Tj 3.811111 0 Td 58.333333 Tz (Inhi ) Tj 51.428571 0 0 51.428571 0 172.322353 Tm 25.277778 0 Td 48.070988 Tz (bition ) Tj 1.827778 0 Td 55.092593 Tz (of ) Tj 0.738889 0 Td 72.592593 Tz (ATXby ) Tj 2.352778 0 Td 71.296296 Tz (LPA ) Tj 1.361111 0 Td 59.41358 Tz (and ) Tj 1.186111 0 Td 65.895062 Tz (S1P ) Tj 1.283333 0 Td 51.041667 Tz (suggests ) Tj 2.566667 0 Td 45.37037 Tz (that ) Tj 1.205556 0 Td 53.240741 Tz (product ) Tj 2.333333 0 Td 55.092593 Tz (feedback ) Tj 1.428571 0 0 1.428571 0 2402 Tm 234.5 0 Td 116.666667 Tz ( ) Tj ET Q endstream endobj 286 0 obj << /Length 1 >> stream q endstream endobj 287 0 obj << /Length 43578 >> stream Q q 0.24 0 0 0.24 0 0 cm BT /F1 1 Tf 3 Tr 62.857143 0 0 62.857143 0 3023 Tm 17.325 0 Td 83.522727 Tz (US ) Tj 1.240909 0 Td 57.154882 Tz (8,497,371 ) Tj 3.388636 0 Td 74.242424 Tz (B2 ) Tj 51.428571 0 0 51.428571 0 2968 Tm 14.875 0 Td 77.777778 Tz (7 ) Tj 51.428571 0 0 51.428571 0 2915.102628 Tm 6.358333 0 Td 46.990741 Tz (inhibition ) Tj 3.091667 0 Td 68.055556 Tz (may ) Tj 1.458333 0 Td 49.907407 Tz (contribute ) Tj 3.227778 0 Td 43.75 Tz (to ) Tj 0.836111 0 Td 47.638889 Tz (regulation ) Tj 3.15 0 Td 58.333333 Tz (of ) Tj 0.816667 0 Td 77.777778 Tz (ATX ) Tj 1.652778 0 Td 50.231481 Tz (function ) Tj 2.663889 0 Td 50.231481 Tz (in ) Tj 51.428571 0 0 51.428571 0 2871.191283 Tm 6.358333 0 Td 47.314815 Tz (vivo. ) Tj 1.613889 0 Td 51.203704 Tz (Additional ) Tj 3.305556 0 Td 49.826389 Tz (reported ) Tj 2.566667 0 Td 76.697531 Tz (ATX ) Tj 1.594444 0 Td 46.018519 Tz (inhibitors ) Tj 2.975 0 Td 50.555556 Tz (share ) Tj 1.711111 0 Td 47.685185 Tz (several ) Tj 2.177778 0 Td 84.259259 Tz (com ) Tj 51.428571 0 0 51.428571 0 2830.479193 Tm 6.358333 0 Td 71.296296 Tz (mon ) Tj 1.652778 0 Td 45.37037 Tz (structural ) Tj 3.072222 0 Td 45.37037 Tz (features, ) Tj 2.8 0 Td 50.771605 Tz (including ) Tj 3.072222 0 Td 55.092593 Tz (a ) Tj 0.641667 0 Td 52.5 Tz (phosphate, ) Tj 3.480556 0 Td 57.118056 Tz (thiophos ) Tj 51.428571 0 0 51.428571 0 2786.492308 Tm 6.358333 0 Td 48.611111 Tz (phate, ) Tj 2.119444 0 Td 53.472222 Tz (or ) Tj 0.913889 0 Td 55.976431 Tz (phosphonate ) Tj 4.005556 0 Td 56.893004 Tz (headgroup ) Tj 3.402778 0 Td 51.041667 Tz (attached ) Tj 2.8 0 Td 46.450617 Tz (either ) Tj 2.002778 0 Td 52.662037 Tz (with ) Tj 1.633333 0 Td 51.851852 Tz (or ) Tj 51.428571 0 0 51.428571 0 2740.40458 Tm 6.338889 0 Td 53.703704 Tz (without ) Tj 2.430556 0 Td 51.851852 Tz (a ) Tj 0.525 0 Td 47.530864 Tz (linker ) Tj 1.886111 0 Td 45.37037 Tz (to ) Tj 0.758333 0 Td 56.712963 Tz (an ) Tj 0.875 0 Td 47.962963 Tz (alkyl ) Tj 1.652778 0 Td 48.611111 Tz (chain, ) Tj 1.944444 0 Td 58.981481 Tz (which ) Tj 1.983333 0 Td 55.092593 Tz (can ) Tj 1.225 0 Td 51.851852 Tz (vary ) Tj 1.458333 0 Td 46.990741 Tz (in ) Tj 0.719444 0 Td 48.148148 Tz (overall ) Tj 51.428571 0 0 51.428571 0 2695.920792 Tm 6.358333 0 Td 50.231481 Tz (length ) Tj 2.022222 0 Td 59.41358 Tz (and ) Tj 1.283333 0 Td 55.092593 Tz (can ) Tj 1.205556 0 Td 58.333333 Tz (be ) Tj 0.894444 0 Td 46.990741 Tz (either ) Tj 1.886111 0 Td 48.611111 Tz (Saturated ) Tj 2.838889 0 Td 53.472222 Tz (or ) Tj 0.816667 0 Td 48.611111 Tz (unsaturated. ) Tj 3.811111 0 Td 55.902778 Tz (However, ) Tj 51.428571 0 0 51.428571 0 2654.428571 Tm 6.338889 0 Td 50.555556 Tz (these ) Tj 1.672222 0 Td 61.574074 Tz (compounds ) Tj 3.461111 0 Td 51.851852 Tz (lack ) Tj 1.341667 0 Td 46.843434 Tz (Substantial ) Tj 3.266667 0 Td 45.046296 Tz (structural ) Tj 2.877778 0 Td 45.730453 Tz (diversity ) Tj 2.644444 0 Td 47.530864 Tz (for ) Tj 0.952778 0 Td 70.216049 Tz (pos ) Tj 51.428571 0 0 51.428571 0 2611.088235 Tm 6.377778 0 Td 44.722222 Tz (sible ) Tj 1.536111 0 Td 48.611111 Tz (additive ) Tj 2.527778 0 Td 53.472222 Tz (or ) Tj 0.816667 0 Td 47.138047 Tz (synergistic ) Tj 3.325 0 Td 46.450617 Tz (effect ) Tj 1.847222 0 Td 45.37037 Tz (at ) Tj 0.758333 0 Td 55.812757 Tz (improving ) Tj 3.188889 0 Td 76.697531 Tz (ATX ) Tj 1.613889 0 Td 60.925926 Tz (reduc ) Tj 51.428571 0 0 51.428571 0 2568.481572 Tm 6.338889 0 Td 43.425926 Tz (tion. ) Tj 1.497222 0 Td 55.092593 Tz (For ) Tj 1.147222 0 Td 46.180556 Tz (oral ) Tj 1.263889 0 Td 49.331276 Tz (ingestion ) Tj 2.8 0 Td 51.49177 Tz (purposes, ) Tj 2.916667 0 Td 50.231481 Tz (as ) Tj 0.777778 0 Td 47.314815 Tz (well, ) Tj 1.575 0 Td 34.027778 Tz (it ) Tj 0.544444 0 Td 38.888889 Tz (is ) Tj 0.661111 0 Td 55.092593 Tz (of ) Tj 0.719444 0 Td 49.259259 Tz (great ) Tj 1.633333 0 Td 64.814815 Tz (impor ) Tj 51.428571 0 0 51.428571 0 2523.508434 Tm 6.338889 0 Td 51.851852 Tz (tance ) Tj 1.711111 0 Td 45.37037 Tz (to ) Tj 0.738889 0 Td 46.585648 Tz (identify ) Tj 2.430556 0 Td 51.203704 Tz (novel ) Tj 1.769444 0 Td 48.611111 Tz (non-lipid ) Tj 2.780556 0 Td 45.694444 Tz (structural ) Tj 2.897222 0 Td 47.685185 Tz (classes ) Tj 2.197222 0 Td 52.777778 Tz (capable ) Tj 2.372222 0 Td 56.712963 Tz (of ) Tj 51.428571 0 0 51.428571 0 2480.191919 Tm 6.358333 0 Td 47.314815 Tz (inhibiting ) Tj 3.091667 0 Td 77.777778 Tz (ATX ) Tj 1.730556 0 Td 46.180556 Tz (that ) Tj 1.4 0 Td 49.691358 Tz (are ) Tj 1.186111 0 Td 45.910494 Tz (structurally ) Tj 3.616667 0 Td 48.611111 Tz (dissimilar ) Tj 3.188889 0 Td 57.523148 Tz (from ) Tj 1.711111 0 Td 51.851852 Tz (those ) Tj 51.428571 0 0 51.428571 0 2437.871194 Tm 6.358333 0 Td 48.251029 Tz (currently ) Tj 2.819444 0 Td 55.092593 Tz (used ) Tj 1.516667 0 Td 48.611111 Tz (for ) Tj 1.011111 0 Td 43.75 Tz (this ) Tj 1.244444 0 Td 51.041667 Tz (purpose. ) Tj 51.428571 0 0 51.428571 0 2392.580563 Tm 7.116667 0 Td 35.648148 Tz (It ) Tj 0.622222 0 Td 38.888889 Tz (is ) Tj 0.641667 0 Td 48.971193 Tz (believed, ) Tj 2.838889 0 Td 53.240741 Tz (without ) Tj 2.411111 0 Td 49.537037 Tz (relying ) Tj 2.255556 0 Td 60.763889 Tz (upon ) Tj 1.633333 0 Td 58.333333 Tz (any ) Tj 1.263889 0 Td 46.180556 Tz (specific ) Tj 2.411111 0 Td 43.75 Tz (scientific ) Tj 51.428571 0 0 51.428571 0 2348.45177 Tm 6.338889 0 Td 45.37037 Tz (basis, ) Tj 1.827778 0 Td 45.37037 Tz (that ) Tj 1.263889 0 Td 48.611111 Tz (the ) Tj 1.011111 0 Td 51.851852 Tz (lack ) Tj 1.380556 0 Td 56.712963 Tz (of ) Tj 0.777778 0 Td 46.090535 Tz (diversity ) Tj 2.683333 0 Td 43.75 Tz (in ) Tj 0.738889 0 Td 49.826389 Tz (reported ) Tj 2.488889 0 Td 78.858025 Tz (ATX ) Tj 1.575 0 Td 44.781145 Tz (inhibitors, ) Tj 3.111111 0 Td 51.851852 Tz (as ) Tj 51.428571 0 0 51.428571 0 2302.711819 Tm 6.358333 0 Td 54.444444 Tz (noted ) Tj 1.886111 0 Td 52.391975 Tz (above, ) Tj 2.158333 0 Td 38.888889 Tz (is ) Tj 0.758333 0 Td 50.231481 Tz (due, ) Tj 1.497222 0 Td 43.75 Tz (in ) Tj 0.816667 0 Td 43.425926 Tz (part, ) Tj 1.575 0 Td 45.37037 Tz (to ) Tj 0.816667 0 Td 49.691358 Tz (the ) Tj 1.147222 0 Td 51.851852 Tz (lack ) Tj 1.497222 0 Td 56.712963 Tz (of ) Tj 0.836111 0 Td 58.333333 Tz (a ) Tj 0.602778 0 Td 50.106838 Tz (characterized ) Tj 51.428571 0 0 51.428571 0 2259.13865 Tm 6.338889 0 Td 51.66122 Tz (three-dimensional ) Tj 5.522222 0 Td 47.530864 Tz (structure ) Tj 2.8 0 Td 59.953704 Tz (of ) Tj 0.894444 0 Td 48.611111 Tz (the ) Tj 1.108333 0 Td 62.654321 Tz (enzyme ) Tj 2.547222 0 Td 37.962963 Tz (itself. ) Tj 1.827778 0 Td 64.814815 Tz (The ) Tj 1.380556 0 Td 77.777778 Tz (ATX ) Tj 51.428571 0 0 51.428571 0 2216.436435 Tm 6.377778 0 Td 55.497685 Tz (sequence ) Tj 2.955556 0 Td 58.333333 Tz (of ) Tj 0.894444 0 Td 55.092593 Tz (over ) Tj 1.575 0 Td 62.654321 Tz (860 ) Tj 1.4 0 Td 59.62963 Tz (amino ) Tj 2.119444 0 Td 49.259259 Tz (acids ) Tj 1.788889 0 Td 38.888889 Tz (is ) Tj 0.777778 0 Td 51.851852 Tz (divided ) Tj 2.488889 0 Td 46.180556 Tz (into ) Tj 1.438889 0 Td 47.685185 Tz (several ) Tj 51.428571 0 0 51.428571 0 2175.093023 Tm 6.358333 0 Td 55.092593 Tz (domains, ) Tj 2.877778 0 Td 50.771605 Tz (including ) Tj 2.975 0 Td 51.851852 Tz (a ) Tj 0.563889 0 Td 46.296296 Tz (central ) Tj 2.177778 0 Td 45.37037 Tz (catalytic ) Tj 2.683333 0 Td 60.493827 Tz (domain ) Tj 2.430556 0 Td 61.168981 Tz (composed ) Tj 3.169444 0 Td 56.712963 Tz (of ) Tj 40 0 0 40 0 2135 Tm 8.175 0 Td 70 Tz (about ) Tj 2.325 0 Td 81.944444 Tz (400 ) Tj 1.725 0 Td 76.666667 Tz (amino ) Tj 2.6 0 Td 59.027778 Tz (acids. ) Tj 2.425 0 Td 97.222222 Tz (ATX ) Tj 2.075 0 Td 50 Tz (is ) Tj 0.9 0 Td 70.833333 Tz (a ) Tj 0.725 0 Td 85.416667 Tz (member ) Tj 3.3 0 Td 75 Tz (of ) Tj 1.1 0 Td 62.5 Tz (the ) Tj 1.4 0 Td 65 Tz (nucleotide ) Tj 51.428571 0 0 51.428571 0 2089.951106 Tm 6.358333 0 Td 52.637486 Tz (pyrophosphatase/phosphodiesterase ) Tj 10.577778 0 Td 60.277778 Tz (\(NPP\) ) Tj 1.983333 0 Td 47.685185 Tz (family, ) Tj 2.119444 0 Td 51.851852 Tz (as ) Tj 0.777778 0 Td 51.041667 Tz (well ) Tj 1.380556 0 Td 51.851852 Tz (as ) Tj 51.428571 0 0 51.428571 0 2045.681293 Tm 6.338889 0 Td 50.771605 Tz (the ) Tj 1.011111 0 Td 48.611111 Tz (alkaline ) Tj 2.45 0 Td 53.914141 Tz (phosphatase ) Tj 3.694444 0 Td 49.421296 Tz (Superfamily. ) Tj 3.694444 0 Td 50.434028 Tz (Crystallographic ) Tj 4.997222 0 Td 54.444444 Tz (struc ) Tj 51.428571 0 0 51.428571 0 1999.482467 Tm 6.338889 0 Td 47.314815 Tz (tures ) Tj 1.691667 0 Td 56.712963 Tz (of ) Tj 0.816667 0 Td 48.148148 Tz (several ) Tj 2.275 0 Td 48.206019 Tz (alkaline ) Tj 2.527778 0 Td 54.208754 Tz (phosphatase ) Tj 3.830556 0 Td 51.851852 Tz (Superfamily ) Tj 3.694444 0 Td 62.962963 Tz (members ) Tj 51.428571 0 0 51.428571 0 1954.019305 Tm 6.338889 0 Td 57.523148 Tz (have ) Tj 1.691667 0 Td 56.712963 Tz (been ) Tj 1.711111 0 Td 48.251029 Tz (available ) Tj 2.955556 0 Td 46.450617 Tz (for ) Tj 1.166667 0 Td 51.041667 Tz (decades. ) Tj 2.8 0 Td 57.685185 Tz (These ) Tj 2.061111 0 Td 45.833333 Tz (crystal ) Tj 2.275 0 Td 46.990741 Tz (structures ) Tj 40 0 0 40 0 1917 Tm 8.2 0 Td 77.083333 Tz (show ) Tj 2.175 0 Td 70 Tz (remarkable ) Tj 4.4 0 Td 58.75 Tz (structural ) Tj 3.775 0 Td 65.625 Tz (conservation ) Tj 5 0 Td 56.25 Tz (in ) Tj 0.925 0 Td 66.666667 Tz (a ) Tj 0.675 0 Td 65.833333 Tz (small ) Tj 2.225 0 Td 65.625 Tz (core ) Tj 1.85 0 Td 77.777778 Tz (Sur ) Tj 51.428571 0 0 51.428571 0 1870.78961 Tm 6.358333 0 Td 54.6875 Tz (rounding ) Tj 2.975 0 Td 49.691358 Tz (the ) Tj 1.263889 0 Td 45.010288 Tz (catalytic ) Tj 2.8 0 Td 39.537037 Tz (site, ) Tj 1.516667 0 Td 52.932099 Tz (but ) Tj 1.283333 0 Td 50.106838 Tz (unfortunately ) Tj 4.258333 0 Td 61.574074 Tz (show ) Tj 1.866667 0 Td 83.179012 Tz (com ) Tj 51.428571 0 0 51.428571 0 1823.004926 Tm 6.358333 0 Td 47.222222 Tz (pletely ) Tj 2.275 0 Td 46.090535 Tz (different ) Tj 2.741667 0 Td 45.694444 Tz (structural ) Tj 3.013889 0 Td 46.234568 Tz (characteristics ) Tj 4.433333 0 Td 50.462963 Tz (outside ) Tj 2.411111 0 Td 42.12963 Tz (this ) Tj 1.302778 0 Td 71.296296 Tz (con ) Tj 51.428571 0 0 51.428571 0 1782.587413 Tm 6.377778 0 Td 51.851852 Tz (served ) Tj 1.983333 0 Td 46.666667 Tz (core. ) Tj 1.555556 0 Td 57.928241 Tz (Sequence ) Tj 2.877778 0 Td 61.168981 Tz (homology ) Tj 3.091667 0 Td 51.851852 Tz (of ) Tj 0.680556 0 Td 49.691358 Tz (the ) Tj 0.991667 0 Td 48.611111 Tz (alkaline ) Tj 2.411111 0 Td 53.472222 Tz (phosphatases ) Tj 40 0 0 40 0 1743 Tm 8.15 0 Td 69.791667 Tz (with ) Tj 1.9 0 Td 100 Tz (ATX ) Tj 2.1 0 Td 69.791667 Tz (does ) Tj 1.95 0 Td 66.666667 Tz (not ) Tj 1.4 0 Td 72.916667 Tz (exceed ) Tj 2.975 0 Td 87.5 Tz (14% ) Tj 1.85 0 Td 76.388889 Tz (and ) Tj 1.625 0 Td 50 Tz (is ) Tj 0.875 0 Td 62.5 Tz (therefore ) Tj 3.65 0 Td 57.986111 Tz (insufficient ) Tj 51.428571 0 0 51.428571 0 1696.692924 Tm 6.358333 0 Td 48.611111 Tz (for ) Tj 1.166667 0 Td 51.203704 Tz (generation ) Tj 3.422222 0 Td 56.712963 Tz (of ) Tj 0.894444 0 Td 58.333333 Tz (a ) Tj 0.661111 0 Td 53.472222 Tz (high ) Tj 1.633333 0 Td 47.685185 Tz (quality ) Tj 2.333333 0 Td 61.168981 Tz (homology ) Tj 3.325 0 Td 58.981481 Tz (model ) Tj 2.119444 0 Td 43.75 Tz (in ) Tj 0.855556 0 Td 59.41358 Tz (any ) Tj 52.857143 0 0 52.857143 0 1650.533648 Tm 6.186486 0 Td 49.399399 Tz (region ) Tj 1.92973 0 Td 49.099099 Tz (outside ) Tj 2.175676 0 Td 50.45045 Tz (the ) Tj 1.021622 0 Td 52.148302 Tz (approximately ) Tj 4.294595 0 Td 55.705706 Tz (100 ) Tj 1.116216 0 Td 58.648649 Tz (amino ) Tj 1.891892 0 Td 50.45045 Tz (acid ) Tj 1.343243 0 Td 44.932432 Tz (structurally ) Tj 51.428571 0 0 51.428571 0 1604.88 Tm 6.358333 0 Td 54.73251 Tz (conserved ) Tj 3.130556 0 Td 47.962963 Tz (core. ) Tj 1.652778 0 Td 63.734568 Tz (The ) Tj 1.361111 0 Td 49.151235 Tz (recent ) Tj 2.002778 0 Td 47.530864 Tz (report ) Tj 1.925 0 Td 58.333333 Tz (of ) Tj 0.797222 0 Td 55.092593 Tz (a ) Tj 0.544444 0 Td 46.296296 Tz (crystal ) Tj 2.158333 0 Td 47.170782 Tz (structure ) Tj 2.761111 0 Td 56.712963 Tz (of ) Tj 0.816667 0 Td 55.092593 Tz (a ) Tj 51.428571 0 0 51.428571 0 1562.423123 Tm 6.338889 0 Td 47.170782 Tz (bacterial ) Tj 2.663889 0 Td 74.537037 Tz (NPP ) Tj 1.458333 0 Td 63.194444 Tz (enzyme ) Tj 2.391667 0 Td 54.282407 Tz (with ) Tj 1.438889 0 Td 73.45679 Tz (30% ) Tj 1.477778 0 Td 46.585648 Tz (identity ) Tj 2.372222 0 Td 45.37037 Tz (to ) Tj 0.7 0 Td 49.691358 Tz (the ) Tj 0.991667 0 Td 76.697531 Tz (ATX ) Tj 1.516667 0 Td 45.730453 Tz (catalytic ) Tj 51.428571 0 0 51.428571 0 1516.813459 Tm 6.358333 0 Td 52.662037 Tz (core ) Tj 1.361111 0 Td 60.493827 Tz (domain ) Tj 2.313889 0 Td 53.240741 Tz (enabled ) Tj 2.372222 0 Td 49.691358 Tz (the ) Tj 1.011111 0 Td 56.565657 Tz (development ) Tj 3.830556 0 Td 55.092593 Tz (of ) Tj 0.738889 0 Td 51.851852 Tz (a ) Tj 0.447222 0 Td 45.046296 Tz (structural ) Tj 2.877778 0 Td 59.62963 Tz (model ) Tj 1.905556 0 Td 58.333333 Tz (of ) Tj 51.428571 0 0 51.428571 0 1474.666667 Tm 6.338889 0 Td 50.771605 Tz (the ) Tj 1.030556 0 Td 77.777778 Tz (ATX ) Tj 1.575 0 Td 45.37037 Tz (catalytic ) Tj 2.644444 0 Td 59.953704 Tz (domain ) Tj 2.333333 0 Td 45.37037 Tz (that ) Tj 1.263889 0 Td 66.975309 Tz (may ) Tj 1.380556 0 Td 55.092593 Tz (prove ) Tj 1.827778 0 Td 48.611111 Tz (useful ) Tj 1.944444 0 Td 43.75 Tz (in ) Tj 0.7 0 Td 51.49177 Tz (structure ) Tj 51.428571 0 0 51.428571 0 1434.368113 Tm 6.338889 0 Td 56.388889 Tz (based ) Tj 1.808333 0 Td 55.902778 Tz (drug ) Tj 1.477778 0 Td 49.074074 Tz (design. ) Tj 2.177778 0 Td 57.118056 Tz (Although ) Tj 2.858333 0 Td 58.333333 Tz (a ) Tj 0.486111 0 Td 45.959596 Tz (significant ) Tj 3.169444 0 Td 55.902778 Tz (improvement, ) Tj 4.180556 0 Td 55.902778 Tz (Such ) Tj 51.428571 0 0 51.428571 0 1387.915094 Tm 6.358333 0 Td 55.092593 Tz (a ) Tj 0.427778 0 Td 61.574074 Tz (homology ) Tj 3.111111 0 Td 59.62963 Tz (model ) Tj 1.925 0 Td 59.143519 Tz (must ) Tj 1.516667 0 Td 58.333333 Tz (be ) Tj 0.797222 0 Td 51.388889 Tz (applied ) Tj 2.294444 0 Td 49.259259 Tz (cautiously ) Tj 3.091667 0 Td 48.611111 Tz (as ) Tj 0.719444 0 Td 54.503367 Tz (involvement ) Tj 51.428571 0 0 51.428571 0 1342.184116 Tm 6.358333 0 Td 58.333333 Tz (of ) Tj 0.777778 0 Td 52.932099 Tz (the ) Tj 1.127778 0 Td 49.583333 Tz (c-terminal ) Tj 3.208333 0 Td 48.860399 Tz (nuclease-like ) Tj 4.005556 0 Td 59.953704 Tz (domain ) Tj 2.372222 0 Td 46.990741 Tz (in ) Tj 0.758333 0 Td 48.251029 Tz (Substrate ) Tj 2.819444 0 Td 56.944444 Tz (recogni ) Tj 51.428571 0 0 51.428571 0 1299.359223 Tm 6.338889 0 Td 47.800926 Tz (tion ) Tj 1.302778 0 Td 54.012346 Tz (has ) Tj 1.127778 0 Td 56.712963 Tz (been ) Tj 1.555556 0 Td 52.932099 Tz (suggested ) Tj 3.033333 0 Td 57.523148 Tz (from ) Tj 1.575 0 Td 47.222222 Tz (studies ) Tj 2.138889 0 Td 58.333333 Tz (of ) Tj 0.777778 0 Td 75.617284 Tz (NPP ) Tj 1.516667 0 Td 51.851852 Tz (family ) Tj 2.061111 0 Td 66.435185 Tz (domain ) Tj 51.428571 0 0 51.428571 0 1257.688645 Tm 6.377778 0 Td 57.928241 Tz (Swapping ) Tj 2.994444 0 Td 51.131687 Tz (chimeras. ) Tj 3.033333 0 Td 46.990741 Tz (In ) Tj 0.777778 0 Td 58.333333 Tz (any ) Tj 1.263889 0 Td 48.611111 Tz (event, ) Tj 1.963889 0 Td 50.555556 Tz (these ) Tj 1.691667 0 Td 51.203704 Tz (previously ) Tj 3.325 0 Td 50.636574 Tz (reported ) Tj 51.428571 0 0 51.428571 0 1213.150617 Tm 6.358333 0 Td 78.858025 Tz (ATX ) Tj 1.633333 0 Td 46.018519 Tz (inhibitors ) Tj 2.975 0 Td 49.691358 Tz (are ) Tj 1.088889 0 Td 52.777778 Tz (analogs ) Tj 2.430556 0 Td 58.333333 Tz (of ) Tj 0.816667 0 Td 60.763889 Tz (LPA, ) Tj 1.672222 0 Td 51.851852 Tz (a ) Tj 0.525 0 Td 51.103989 Tz (phospholipid, ) Tj 4.161111 0 Td 60.493827 Tz (and ) Tj 1.263889 0 Td 50.771605 Tz (are ) Tj 51.428571 0 0 51.428571 0 1170.42654 Tm 6.358333 0 Td 61.574074 Tz (more ) Tj 1.613889 0 Td 55.387205 Tz (hydrophobic ) Tj 3.811111 0 Td 51.041667 Tz (than ) Tj 1.380556 0 Td 37.268519 Tz (is ) Tj 0.583333 0 Td 46.759259 Tz (typical ) Tj 2.080556 0 Td 55.092593 Tz (of ) Tj 0.738889 0 Td 47.530864 Tz (orally ) Tj 1.827778 0 Td 48.881173 Tz (bioavailable ) Tj 3.655556 0 Td 48.611111 Tz (drugs, ) Tj 51.428571 0 0 51.428571 0 1127.631879 Tm 6.338889 0 Td 52.314815 Tz (thereby ) Tj 2.411111 0 Td 48.206019 Tz (creating ) Tj 2.488889 0 Td 56.30787 Tz (problems ) Tj 2.897222 0 Td 46.990741 Tz (in ) Tj 0.738889 0 Td 46.180556 Tz (that ) Tj 1.283333 0 Td 45.37037 Tz (area. ) Tj 51.428571 0 0 51.428571 0 1080.451815 Tm 7.097222 0 Td 66.435185 Tz (As ) Tj 0.952778 0 Td 48.611111 Tz (such, ) Tj 1.633333 0 Td 48.611111 Tz (there ) Tj 1.575 0 Td 45.37037 Tz (exists ) Tj 1.769444 0 Td 55.092593 Tz (a ) Tj 0.466667 0 Td 45.37037 Tz (definitive ) Tj 2.838889 0 Td 51.041667 Tz (lack ) Tj 1.341667 0 Td 46.990741 Tz (in ) Tj 0.7 0 Td 52.211934 Tz (providing ) Tj 2.936111 0 Td 46.8107 Tz (effective ) Tj 51.428571 0 0 51.428571 0 1035 Tm 6.358333 0 Td 78.858025 Tz (ATX ) Tj 1.691667 0 Td 46.666667 Tz (inhibition ) Tj 3.111111 0 Td 47.530864 Tz (\(or ) Tj 1.108333 0 Td 46.616809 Tz (inactivation\) ) Tj 3.927778 0 Td 50.231481 Tz (within ) Tj 2.1 0 Td 49.691358 Tz (the ) Tj 1.147222 0 Td 49.537037 Tz (current ) Tj 2.333333 0 Td 68.055556 Tz (knowl ) Tj 51.428571 0 0 51.428571 0 995.058537 Tm 6.358333 0 Td 57.523148 Tz (edge ) Tj 1.516667 0 Td 55.092593 Tz (base ) Tj 1.497222 0 Td 43.75 Tz (in ) Tj 0.719444 0 Td 42.939815 Tz (this ) Tj 1.186111 0 Td 47.314815 Tz (area, ) Tj 1.555556 0 Td 46.720679 Tz (particularly ) Tj 3.538889 0 Td 50.231481 Tz (as ) Tj 0.797222 0 Td 32.407407 Tz (it ) Tj 0.563889 0 Td 53.472222 Tz (concerns ) Tj 2.741667 0 Td 61.934156 Tz (compounds ) Tj 51.428571 0 0 51.428571 0 950.195122 Tm 6.338889 0 Td 46.990741 Tz (that ) Tj 1.302778 0 Td 50.771605 Tz (not ) Tj 1.030556 0 Td 54.282407 Tz (only ) Tj 1.438889 0 Td 48.611111 Tz (exhibit ) Tj 2.158333 0 Td 77.777778 Tz (ATX ) Tj 1.575 0 Td 45.37037 Tz (inhibition, ) Tj 3.15 0 Td 50.771605 Tz (but ) Tj 1.088889 0 Td 56.712963 Tz (do ) Tj 0.855556 0 Td 53.472222 Tz (so ) Tj 0.797222 0 Td 46.548822 Tz (selectively ) Tj 3.266667 0 Td 47.530864 Tz (for ) Tj 51.428571 0 0 51.428571 0 908.557457 Tm 6.358333 0 Td 70.486111 Tz (NPP2 ) Tj 1.925 0 Td 48.611111 Tz (alone, ) Tj 1.963889 0 Td 50.231481 Tz (as ) Tj 0.816667 0 Td 60.358796 Tz (compared ) Tj 3.111111 0 Td 52.662037 Tz (with ) Tj 1.516667 0 Td 51.203704 Tz (other ) Tj 1.75 0 Td 58.738426 Tz (NPP-type ) Tj 3.033333 0 Td 61.934156 Tz (compounds ) Tj 51.428571 0 0 51.428571 0 860.945107 Tm 6.377778 0 Td 63.518519 Tz (\(NPP6 ) Tj 2.061111 0 Td 59.41358 Tz (and ) Tj 1.244444 0 Td 62.222222 Tz (NPP7, ) Tj 2.022222 0 Td 48.611111 Tz (for ) Tj 1.030556 0 Td 46.342593 Tz (instance\). ) Tj 2.916667 0 Td 63.734568 Tz (The ) Tj 1.302778 0 Td 51.851852 Tz (determination ) Tj 4.2 0 Td 56.712963 Tz (of ) Tj 0.777778 0 Td 53.472222 Tz (proper ) Tj 51.428571 0 0 51.428571 0 820.668246 Tm 6.377778 0 Td 46.450617 Tz (selective ) Tj 2.625 0 Td 70.486111 Tz (NPP2 ) Tj 1.847222 0 Td 47.314815 Tz (inhibiting ) Tj 2.916667 0 Td 62.294239 Tz (compounds ) Tj 3.5 0 Td 56.018519 Tz (canthus ) Tj 2.488889 0 Td 49.691358 Tz (aid ) Tj 1.05 0 Td 43.75 Tz (in ) Tj 0.7 0 Td 50.771605 Tz (not ) Tj 1.011111 0 Td 55.092593 Tz (only ) Tj 51.428571 0 0 51.428571 0 775.735363 Tm 6.358333 0 Td 47.685185 Tz (further ) Tj 2.119444 0 Td 50.501543 Tz (optimization ) Tj 3.791667 0 Td 53.472222 Tz (of ) Tj 0.719444 0 Td 49.691358 Tz (autotaxin ) Tj 2.780556 0 Td 51.49177 Tz (treatment ) Tj 2.877778 0 Td 48.611111 Tz (agents, ) Tj 2.177778 0 Td 50.771605 Tz (but ) Tj 1.011111 0 Td 48.611111 Tz (also ) Tj 1.283333 0 Td 61.574074 Tz (an ) Tj 51.428571 0 0 51.428571 0 732.048077 Tm 6.338889 0 Td 53.098291 Tz (understanding ) Tj 4.336111 0 Td 58.333333 Tz (of ) Tj 0.777778 0 Td 50.771605 Tz (the ) Tj 1.088889 0 Td 48.611111 Tz (actual ) Tj 1.925 0 Td 60.925926 Tz (amino ) Tj 2.002778 0 Td 51.851852 Tz (acid ) Tj 1.458333 0 Td 46.666667 Tz (structures ) Tj 2.994444 0 Td 50.462963 Tz (outside ) Tj 2.313889 0 Td 56.712963 Tz (of ) Tj 51.428571 0 0 51.428571 0 687.335045 Tm 6.338889 0 Td 50.771605 Tz (the ) Tj 1.166667 0 Td 77.777778 Tz (ATX ) Tj 1.691667 0 Td 50.501543 Tz (conservative ) Tj 3.908333 0 Td 46.666667 Tz (core. ) Tj 1.691667 0 Td 64.814815 Tz (As ) Tj 1.108333 0 Td 49.259259 Tz (such, ) Tj 1.769444 0 Td 52.662037 Tz (although ) Tj 2.858333 0 Td 63.194444 Tz (some ) Tj 1.788889 0 Td 83.179012 Tz (com ) Tj 51.428571 0 0 51.428571 0 646.821516 Tm 6.358333 0 Td 58.333333 Tz (pounds ) Tj 2.313889 0 Td 66.975309 Tz (may ) Tj 1.4 0 Td 57.87037 Tz (promote ) Tj 2.586111 0 Td 77.777778 Tz (ATX ) Tj 1.613889 0 Td 46.342593 Tz (inhibition ) Tj 2.975 0 Td 50.231481 Tz (as ) Tj 0.777778 0 Td 51.851852 Tz (they ) Tj 1.458333 0 Td 48.251029 Tz (currently ) Tj 2.780556 0 Td 42.669753 Tz (exist, ) Tj 51.428571 0 0 51.428571 0 600.804878 Tm 6.377778 0 Td 63.194444 Tz (Some ) Tj 1.691667 0 Td 48.611111 Tz (others ) Tj 1.925 0 Td 53.472222 Tz (with ) Tj 1.458333 0 Td 59.953704 Tz (homologous ) Tj 3.752778 0 Td 46.990741 Tz (structures ) Tj 3.013889 0 Td 42.12963 Tz (\(at ) Tj 0.913889 0 Td 44.722222 Tz (least ) Tj 1.497222 0 Td 45.37037 Tz (to ) Tj 0.738889 0 Td 55.092593 Tz (a ) Tj 0.486111 0 Td 47.685185 Tz (certain ) Tj 51.428571 0 0 51.428571 0 557.62439 Tm 6.358333 0 Td 51.388889 Tz (degree\) ) Tj 2.313889 0 Td 48.611111 Tz (to ) Tj 0.758333 0 Td 55.092593 Tz (such ) Tj 1.516667 0 Td 46.450617 Tz (effective ) Tj 2.625 0 Td 78.858025 Tz (ATX ) Tj 1.575 0 Td 50.771605 Tz (reduction ) Tj 2.916667 0 Td 51.851852 Tz (agents ) Tj 2.080556 0 Td 66.975309 Tz (may ) Tj 1.380556 0 Td 51.203704 Tz (serve ) Tj 1.691667 0 Td 50.231481 Tz (as ) Tj 51.428571 0 0 51.428571 0 512.647904 Tm 6.358333 0 Td 50.771605 Tz (intermediate ) Tj 3.85 0 Td 61.934156 Tz (compounds ) Tj 3.577778 0 Td 48.611111 Tz (for ) Tj 1.069444 0 Td 47.685185 Tz (further ) Tj 2.216667 0 Td 48.206019 Tz (reaction ) Tj 2.508333 0 Td 53.472222 Tz (and/or ) Tj 2.119444 0 Td 58.873457 Tz (modifi ) Tj 51.428571 0 0 51.428571 0 472.521101 Tm 6.358333 0 Td 49.151235 Tz (cation ) Tj 1.963889 0 Td 48.611111 Tz (for ) Tj 1.05 0 Td 54.282407 Tz (Such ) Tj 1.497222 0 Td 55.092593 Tz (an ) Tj 0.875 0 Td 50.771605 Tz (optimization ) Tj 3.85 0 Td 48.611111 Tz (process. ) Tj 51.428571 0 0 51.428571 0 426.549561 Tm 7.097222 0 Td 66.435185 Tz (As ) Tj 0.972222 0 Td 53.148148 Tz (noted ) Tj 1.75 0 Td 52.391975 Tz (above, ) Tj 2.041667 0 Td 51.851852 Tz (previous ) Tj 2.644444 0 Td 51.041667 Tz (attempts ) Tj 2.625 0 Td 45.37037 Tz (at ) Tj 0.680556 0 Td 55.092593 Tz (Such ) Tj 1.477778 0 Td 50.555556 Tz (treatments ) Tj 3.169444 0 Td 57.523148 Tz (have ) Tj 51.428571 0 0 51.428571 0 384.855107 Tm 6.358333 0 Td 53.877315 Tz (provided ) Tj 2.761111 0 Td 55.362654 Tz (developments ) Tj 4.180556 0 Td 58.333333 Tz (of ) Tj 0.777778 0 Td 46.759259 Tz (certain ) Tj 2.158333 0 Td 47.685185 Tz (classes ) Tj 2.216667 0 Td 55.092593 Tz (of ) Tj 0.738889 0 Td 62.294239 Tz (compounds ) Tj 3.538889 0 Td 46.180556 Tz (that ) Tj 48.571429 0 0 48.571429 0 339 Tm 6.732353 0 Td 50.980392 Tz (exhibit ) Tj 2.285294 0 Td 49.509804 Tz (certain ) Tj 2.264706 0 Td 52.941176 Tz (desired ) Tj 2.367647 0 Td 47.54902 Tz (results ) Tj 2.161765 0 Td 56.617647 Tz (with ) Tj 1.482353 0 Td 57.352941 Tz (ATXinhibition. ) Tj 5.044118 0 Td 59.620098 Tz (However, ) Tj 51.428571 0 0 51.428571 0 297.216749 Tm 6.338889 0 Td 50.771605 Tz (the ) Tj 1.166667 0 Td 50.87963 Tz (generation ) Tj 3.325 0 Td 58.333333 Tz (of ) Tj 0.836111 0 Td 48.148148 Tz (classes ) Tj 2.313889 0 Td 44.560185 Tz (that ) Tj 1.322222 0 Td 46.254209 Tz (effectively ) Tj 3.305556 0 Td 52.777778 Tz (provide ) Tj 2.488889 0 Td 51.131687 Tz (increased ) Tj 51.428571 0 0 51.428571 0 252.066026 Tm 6.358333 0 Td 46.759259 Tz (overall ) Tj 2.119444 0 Td 77.777778 Tz (ATX ) Tj 1.575 0 Td 46.342593 Tz (inhibition ) Tj 2.936111 0 Td 46.234568 Tz (characteristics ) Tj 4.316667 0 Td 52.932099 Tz (has ) Tj 1.108333 0 Td 56.712963 Tz (been ) Tj 1.516667 0 Td 51.388889 Tz (lacking ) Tj 2.313889 0 Td 43.75 Tz (in ) Tj 0.7 0 Td 49.691358 Tz (the ) Tj 51.428571 0 0 51.428571 0 215.659929 Tm 6.358333 0 Td 52.777778 Tz (pharmaceutical ) Tj 4.647222 0 Td 46.090535 Tz (industry. ) Tj 2.663889 0 Td 64.814815 Tz (The ) Tj 1.322222 0 Td 50.925926 Tz (present ) Tj 2.313889 0 Td 50.05144 Tz (invention ) Tj 2.877778 0 Td 52.256944 Tz (provides ) Tj 2.741667 0 Td 50.771605 Tz (not ) Tj 51.428571 0 0 51.428571 0 174.814815 Tm 6.358333 0 Td 53.472222 Tz (only ) Tj 1.438889 0 Td 57.118056 Tz (improved ) Tj 2.819444 0 Td 55.840456 Tz (ATXinhibiting ) Tj 4.472222 0 Td 58.657407 Tz (compounds, ) Tj 3.636111 0 Td 51.851852 Tz (but ) Tj 1.011111 0 Td 50.231481 Tz (possible ) Tj 2.527778 0 Td 51.851852 Tz (inter ) Tj 30 0 0 30 0 2547 Tm 41.666667 0 Td 75 Tz (10 ) Tj 30 0 0 30 0 2339 Tm 41.666667 0 Td 63.888889 Tz (15 ) Tj 30 0 0 30 0 1923 Tm 41.6 0 Td 77.777778 Tz (25 ) Tj 30 0 0 30 0 1716 Tm 41.6 0 Td 80.555556 Tz (30 ) Tj 30 0 0 30 0 1507 Tm 41.6 0 Td 77.777778 Tz (35 ) Tj 30 0 0 30 0 1299 Tm 41.566667 0 Td 83.333333 Tz (40 ) Tj 30 0 0 30 0 1091 Tm 41.566667 0 Td 80.555556 Tz (45 ) Tj 30 0 0 30 0 883 Tm 41.6 0 Td 80.555556 Tz (50 ) Tj 30 0 0 30 0 675 Tm 41.6 0 Td 77.777778 Tz (55 ) Tj 30 0 0 30 0 467 Tm 41.633333 0 Td 77.777778 Tz (60 ) Tj 30 0 0 30 0 259 Tm 41.633333 0 Td 75 Tz (65 ) Tj 52.857143 0 0 52.857143 0 2968 Tm 32.881081 0 Td 72.522523 Tz (8 ) Tj 51.428571 0 0 51.428571 0 2917.879227 Tm 25.297222 0 Td 53.472222 Tz (mediates ) Tj 2.761111 0 Td 51.851852 Tz (as ) Tj 0.816667 0 Td 53.292181 Tz (launching ) Tj 3.072222 0 Td 55.092593 Tz (pads ) Tj 1.536111 0 Td 46.180556 Tz (into ) Tj 1.341667 0 Td 47.222222 Tz (further ) Tj 2.138889 0 Td 58.627946 Tz (improvement ) Tj 4.044444 0 Td 58.333333 Tz (possi ) Tj 40 0 0 40 0 2878 Tm 32.5 0 Td 53.125 Tz (bilities ) Tj 2.825 0 Td 65.277778 Tz (within ) Tj 2.625 0 Td 55.208333 Tz (this ) Tj 1.55 0 Td 65.625 Tz (area ) Tj 1.775 0 Td 64.583333 Tz (as ) Tj 1.05 0 Td 60 Tz (well. ) Tj 38.571429 0 0 38.571429 0 2796 Tm 35.544444 0 Td 105.432099 Tz (ADVANTAGES ) Tj 6.559259 0 Td 115.226337 Tz (AND ) Tj 2.359259 0 Td 89.012346 Tz (BRIEF ) Tj 2.981481 0 Td 94.668911 Tz (DESCRIPTION ) Tj 6.533333 0 Td 99.382716 Tz (OF ) Tj 38.571429 0 0 38.571429 0 2753 Tm 41.637037 0 Td 105.144033 Tz (THE ) Tj 2.177778 0 Td 98.422497 Tz (INVENTION ) Tj 51.428571 0 0 51.428571 0 2661.916449 Tm 26.036111 0 Td 37.268519 Tz (It ) Tj 0.641667 0 Td 37.268519 Tz (is ) Tj 0.641667 0 Td 49.421296 Tz (thus ) Tj 1.419444 0 Td 55.092593 Tz (an ) Tj 0.855556 0 Td 54.73251 Tz (advantage ) Tj 3.130556 0 Td 58.333333 Tz (of ) Tj 0.777778 0 Td 50.771605 Tz (the ) Tj 1.088889 0 Td 50.462963 Tz (present ) Tj 2.313889 0 Td 49.691358 Tz (invention ) Tj 2.877778 0 Td 46.990741 Tz (to ) Tj 0.758333 0 Td 52.777778 Tz (provide ) Tj 51.428571 0 0 51.428571 0 2614.955975 Tm 25.297222 0 Td 45.775463 Tz (reliable ) Tj 2.45 0 Td 60.493827 Tz (and ) Tj 1.380556 0 Td 51.311728 Tz (highly ) Tj 2.119444 0 Td 46.8107 Tz (effective ) Tj 2.819444 0 Td 49.691358 Tz (autotaxin ) Tj 3.013889 0 Td 46.450617 Tz (inactivators ) Tj 3.655556 0 Td 48.611111 Tz (for ) Tj 1.147222 0 Td 49.691358 Tz (the ) Tj 51.428571 0 0 51.428571 0 2573.60396 Tm 25.297222 0 Td 55.092593 Tz (purpose ) Tj 2.488889 0 Td 59.953704 Tz (of ) Tj 0.875 0 Td 52.256944 Tz (reducing ) Tj 2.722222 0 Td 49.691358 Tz (the ) Tj 1.088889 0 Td 52.5 Tz (conversion ) Tj 3.344444 0 Td 61.574074 Tz (of ) Tj 0.875 0 Td 72.376543 Tz (LPC ) Tj 1.516667 0 Td 45.37037 Tz (to ) Tj 0.797222 0 Td 71.296296 Tz (LPA ) Tj 1.516667 0 Td 53.703704 Tz (through ) Tj 51.428571 0 0 51.428571 0 2530.099526 Tm 25.277778 0 Td 50.771605 Tz (the ) Tj 1.030556 0 Td 44.486532 Tz (utilization ) Tj 3.072222 0 Td 55.092593 Tz (of ) Tj 0.738889 0 Td 55.092593 Tz (a ) Tj 0.466667 0 Td 47.222222 Tz (readily ) Tj 2.1 0 Td 48.611111 Tz (available ) Tj 2.741667 0 Td 59.41358 Tz (and ) Tj 1.186111 0 Td 46.450617 Tz (easily ) Tj 1.827778 0 Td 56.30787 Tz (produced ) Tj 2.8 0 Td 84.259259 Tz (com ) Tj 51.428571 0 0 51.428571 0 2488.213155 Tm 25.297222 0 Td 60.925926 Tz (pound ) Tj 2.022222 0 Td 48.611111 Tz (\(or ) Tj 1.05 0 Td 56.860269 Tz (compounds\). ) Tj 3.947222 0 Td 57.87037 Tz (Another ) Tj 2.586111 0 Td 54.73251 Tz (advantage ) Tj 3.15 0 Td 42.12963 Tz (is ) Tj 0.7 0 Td 49.691358 Tz (the ) Tj 1.088889 0 Td 44.444444 Tz (ability ) Tj 2.1 0 Td 47.530864 Tz (for ) Tj 51.428571 0 0 51.428571 0 2442.176755 Tm 25.277778 0 Td 51.49177 Tz (treatment ) Tj 2.975 0 Td 52.662037 Tz (with ) Tj 1.477778 0 Td 55.092593 Tz (Such ) Tj 1.536111 0 Td 61.574074 Tz (compounds ) Tj 3.558333 0 Td 47.530864 Tz (for ) Tj 1.05 0 Td 52.932099 Tz (cancer ) Tj 2.080556 0 Td 50.87963 Tz (prevention ) Tj 3.247222 0 Td 51.851852 Tz (treat ) Tj 51.428571 0 0 51.428571 0 2400.970588 Tm 25.297222 0 Td 60.763889 Tz (ment ) Tj 1.672222 0 Td 51.851852 Tz (regimens. ) Tj 2.955556 0 Td 55.092593 Tz (Yet ) Tj 1.205556 0 Td 52.314815 Tz (another ) Tj 2.372222 0 Td 54.73251 Tz (advantage ) Tj 3.169444 0 Td 37.268519 Tz (is ) Tj 0.641667 0 Td 50.771605 Tz (the ) Tj 1.127778 0 Td 46.8107 Tz (potential ) Tj 2.741667 0 Td 65.625 Tz (capa ) Tj 51.428571 0 0 51.428571 0 2355.723977 Tm 25.277778 0 Td 42.669753 Tz (bility ) Tj 1.691667 0 Td 56.712963 Tz (of ) Tj 0.758333 0 Td 52.572016 Tz (providing ) Tj 2.975 0 Td 54.282407 Tz (combinations ) Tj 4.044444 0 Td 58.333333 Tz (of ) Tj 0.777778 0 Td 46.090535 Tz (different ) Tj 2.644444 0 Td 62.294239 Tz (compounds ) Tj 3.5 0 Td 46.180556 Tz (that ) Tj 51.428571 0 0 51.428571 0 2309.27205 Tm 25.297222 0 Td 49.691358 Tz (are ) Tj 1.108333 0 Td 48.611111 Tz (similar ) Tj 2.216667 0 Td 45.37037 Tz (in ) Tj 0.758333 0 Td 50.771605 Tz (foundational ) Tj 3.908333 0 Td 46.8107 Tz (structure ) Tj 2.702778 0 Td 46.990741 Tz (that ) Tj 1.341667 0 Td 69.135802 Tz (may ) Tj 1.438889 0 Td 48.148148 Tz (exhibit ) Tj 2.197222 0 Td 58.333333 Tz (a ) Tj 0.544444 0 Td 69.135802 Tz (syn ) Tj 51.428571 0 0 51.428571 0 2267.611183 Tm 25.297222 0 Td 44.155093 Tz (ergistic ) Tj 2.469444 0 Td 46.450617 Tz (effect ) Tj 2.041667 0 Td 47.530864 Tz (for ) Tj 1.205556 0 Td 47.222222 Tz (further ) Tj 2.313889 0 Td 57.523148 Tz (improved ) Tj 3.091667 0 Td 77.777778 Tz (ATX ) Tj 1.788889 0 Td 44.781145 Tz (inhibition. ) Tj 3.344444 0 Td 40.185185 Tz (Still ) Tj 51.428571 0 0 51.428571 0 2223.41769 Tm 25.297222 0 Td 52.777778 Tz (another ) Tj 2.391667 0 Td 54.372428 Tz (advantage ) Tj 3.130556 0 Td 38.888889 Tz (is ) Tj 0.719444 0 Td 48.611111 Tz (the ) Tj 1.069444 0 Td 43.981481 Tz (ability ) Tj 2.080556 0 Td 45.37037 Tz (to ) Tj 0.777778 0 Td 54.012346 Tz (determine ) Tj 3.072222 0 Td 46.450617 Tz (effective ) Tj 2.702778 0 Td 63.194444 Tz (auto ) Tj 51.428571 0 0 51.428571 0 2178.158831 Tm 25.277778 0 Td 48.611111 Tz (taxin ) Tj 1.769444 0 Td 45.694444 Tz (inhibitors ) Tj 3.052778 0 Td 52.777778 Tz (through ) Tj 2.527778 0 Td 48.611111 Tz (the ) Tj 1.147222 0 Td 44.486532 Tz (utilization ) Tj 3.188889 0 Td 59.953704 Tz (of ) Tj 0.894444 0 Td 51.851852 Tz (a ) Tj 0.583333 0 Td 54.282407 Tz (base ) Tj 1.594444 0 Td 45.694444 Tz (identified ) Tj 51.428571 0 0 51.428571 0 2139.131673 Tm 25.297222 0 Td 64.00463 Tz (compound ) Tj 3.286111 0 Td 47.530864 Tz (via ) Tj 1.030556 0 Td 50.501543 Tz (intermediate ) Tj 3.791667 0 Td 61.934156 Tz (compounds ) Tj 3.558333 0 Td 64.814815 Tz (made ) Tj 1.691667 0 Td 52.932099 Tz (therefrom ) Tj 3.052778 0 Td 59.41358 Tz (and ) Tj 51.428571 0 0 51.428571 0 2099.487298 Tm 25.297222 0 Td 49.259259 Tz (exhibiting ) Tj 3.052778 0 Td 51.203704 Tz (acceptable ) Tj 3.188889 0 Td 76.697531 Tz (ATX ) Tj 1.497222 0 Td 47.314815 Tz (inhibition ) Tj 2.936111 0 Td 46.843434 Tz (properties, ) Tj 3.188889 0 Td 59.41358 Tz (and ) Tj 1.166667 0 Td 50.636574 Tz (building ) Tj 51.428571 0 0 51.428571 0 2059.744304 Tm 25.297222 0 Td 50.378788 Tz (prospective ) Tj 3.772222 0 Td 61.574074 Tz (compounds ) Tj 3.733333 0 Td 54.166667 Tz (through ) Tj 2.702778 0 Td 55.555556 Tz (pendant ) Tj 2.741667 0 Td 56.388889 Tz (group ) Tj 2.119444 0 Td 50.231481 Tz (addition ) Tj 51.428571 0 0 51.428571 0 2015.458087 Tm 25.277778 0 Td 54.166667 Tz (through ) Tj 2.45 0 Td 46.090535 Tz (different ) Tj 2.663889 0 Td 57.87037 Tz (methods ) Tj 2.605556 0 Td 35.648148 Tz (\(i.e., ) Tj 1.458333 0 Td 53.098291 Tz (computational ) Tj 4.336111 0 Td 51.131687 Tz (Screening ) Tj 2.897222 0 Td 60.493827 Tz (and ) Tj 51.428571 0 0 51.428571 0 1974.381166 Tm 25.316667 0 Td 47.890947 Tz (synthetic ) Tj 2.8 0 Td 52.572016 Tz (medicinal ) Tj 3.052778 0 Td 49.200337 Tz (chemistry\). ) Tj 51.428571 0 0 51.428571 0 1932.137931 Tm 26.016667 0 Td 52.391975 Tz (Accordingly, ) Tj 4.102778 0 Td 43.75 Tz (this ) Tj 1.438889 0 Td 49.331276 Tz (invention ) Tj 2.994444 0 Td 57.744108 Tz (encompasses ) Tj 4.161111 0 Td 55.092593 Tz (a ) Tj 0.719444 0 Td 59.41358 Tz (method ) Tj 2.469444 0 Td 49.691358 Tz (for ) Tj 51.428571 0 0 51.428571 0 1889.736913 Tm 25.297222 0 Td 53.06713 Tz (reducing ) Tj 2.897222 0 Td 50.05144 Tz (autotaxin ) Tj 3.033333 0 Td 45.37037 Tz (activity ) Tj 2.547222 0 Td 45.37037 Tz (to ) Tj 0.933333 0 Td 56.712963 Tz (modify ) Tj 2.469444 0 Td 72.376543 Tz (LPC ) Tj 1.652778 0 Td 45.37037 Tz (to ) Tj 0.933333 0 Td 60.763889 Tz (LPA, ) Tj 1.847222 0 Td 48.611111 Tz (said ) Tj 51.428571 0 0 51.428571 0 1846.394314 Tm 25.297222 0 Td 60.493827 Tz (method ) Tj 2.391667 0 Td 50.771605 Tz (involving ) Tj 2.936111 0 Td 49.691358 Tz (the ) Tj 1.088889 0 Td 48.611111 Tz (reaction ) Tj 2.547222 0 Td 56.712963 Tz (of ) Tj 0.797222 0 Td 49.691358 Tz (autotaxin ) Tj 2.916667 0 Td 52.662037 Tz (with ) Tj 1.458333 0 Td 46.990741 Tz (at ) Tj 0.738889 0 Td 44.722222 Tz (least ) Tj 1.536111 0 Td 58.333333 Tz (one ) Tj 51.428571 0 0 51.428571 0 1807.033613 Tm 25.297222 0 Td 53.652263 Tz (pipemidic ) Tj 3.033333 0 Td 51.851852 Tz (acid ) Tj 1.380556 0 Td 47.638889 Tz (derivative ) Tj 3.013889 0 Td 59.41358 Tz (compound. ) Tj 3.422222 0 Td 45.37037 Tz (In ) Tj 0.7 0 Td 49.074074 Tz (greater ) Tj 2.197222 0 Td 41.666667 Tz (detail. ) Tj 1.925 0 Td 54.282407 Tz (Such ) Tj 1.477778 0 Td 55.092593 Tz (a ) Tj 51.428571 0 0 51.428571 0 1763.890378 Tm 25.277778 0 Td 51.49177 Tz (treatment ) Tj 3.013889 0 Td 59.41358 Tz (method ) Tj 2.352778 0 Td 60.277778 Tz (would ) Tj 2.022222 0 Td 50 Tz (involve ) Tj 2.275 0 Td 58.333333 Tz (a ) Tj 0.544444 0 Td 48.611111 Tz (reaction ) Tj 2.527778 0 Td 53.703704 Tz (product ) Tj 2.45 0 Td 56.712963 Tz (of ) Tj 0.777778 0 Td 63.194444 Tz (pipe ) Tj 51.428571 0 0 51.428571 0 1724.986233 Tm 25.297222 0 Td 55.092593 Tz (midic ) Tj 1.925 0 Td 51.041667 Tz (acid ) Tj 1.458333 0 Td 60.493827 Tz (and ) Tj 1.341667 0 Td 55.092593 Tz (a ) Tj 0.602778 0 Td 51.851852 Tz (phenylthiourea ) Tj 4.647222 0 Td 59.41358 Tz (compound. ) Tj 3.519444 0 Td 64.814815 Tz (More ) Tj 1.847222 0 Td 50.462963 Tz (specifi ) Tj 51.428571 0 0 51.428571 0 1682.454106 Tm 25.297222 0 Td 42.669753 Tz (cally, ) Tj 1.730556 0 Td 48.611111 Tz (the ) Tj 1.108333 0 Td 47.800926 Tz (reaction ) Tj 2.488889 0 Td 53.703704 Tz (product ) Tj 2.45 0 Td 59.62963 Tz (would ) Tj 1.983333 0 Td 45.37037 Tz (exhibit, ) Tj 2.352778 0 Td 47.43266 Tz (preferably, ) Tj 3.325 0 Td 56.712963 Tz (though ) Tj 52.857143 0 0 52.857143 0 1640.363636 Tm 24.613514 0 Td 50.45045 Tz (not ) Tj 1.116216 0 Td 44.932432 Tz (necessarily, ) Tj 3.405405 0 Td 44.144144 Tz (at ) Tj 0.718919 0 Td 42.882883 Tz (least ) Tj 1.437838 0 Td 57.807808 Tz (one ) Tj 1.210811 0 Td 53.603604 Tz (pendant ) Tj 2.383784 0 Td 54.864865 Tz (group ) Tj 1.854054 0 Td 58.333333 Tz (on ) Tj 0.889189 0 Td 48.348348 Tz (the ) Tj 1.040541 0 Td 48.085586 Tz (ring ) Tj 1.305405 0 Td 56.756757 Tz (of ) Tj 0.756757 0 Td 49.399399 Tz (the ) Tj 51.428571 0 0 51.428571 0 1598.176039 Tm 25.297222 0 Td 51.851852 Tz (phenylthiourea ) Tj 4.569444 0 Td 48.206019 Tz (reactant ) Tj 2.547222 0 Td 43.75 Tz (in ) Tj 0.758333 0 Td 49.691358 Tz (the ) Tj 1.147222 0 Td 50.605413 Tz (meta-position ) Tj 4.161111 0 Td 46.990741 Tz (to ) Tj 0.797222 0 Td 49.691358 Tz (the ) Tj 1.088889 0 Td 50.231481 Tz (thiourea ) Tj 51.428571 0 0 51.428571 0 1556.332521 Tm 25.297222 0 Td 49.074074 Tz (linking ) Tj 2.255556 0 Td 55.740741 Tz (group ) Tj 1.866667 0 Td 46.990741 Tz (to ) Tj 0.758333 0 Td 50.771605 Tz (the ) Tj 1.069444 0 Td 54.012346 Tz (pipemidic ) Tj 3.111111 0 Td 51.041667 Tz (acid ) Tj 1.4 0 Td 46.720679 Tz (constituent. ) Tj 3.558333 0 Td 63.734568 Tz (The ) Tj 1.341667 0 Td 58.333333 Tz (follow ) Tj 51.428571 0 0 51.428571 0 1515.647713 Tm 25.297222 0 Td 50.771605 Tz (ing ) Tj 1.166667 0 Td 46.450617 Tz (figure ) Tj 1.866667 0 Td 51.851852 Tz (provides ) Tj 2.702778 0 Td 58.333333 Tz (a ) Tj 0.544444 0 Td 48.37963 Tz (representative ) Tj 4.277778 0 Td 48.206019 Tz (reaction ) Tj 2.527778 0 Td 46.990741 Tz (in ) Tj 0.758333 0 Td 44.560185 Tz (this ) Tj 1.302778 0 Td 54.62963 Tz (manner, ) Tj 52.857143 0 0 52.857143 0 1472.251232 Tm 24.594595 0 Td 54.954955 Tz (wherein ) Tj 2.516216 0 Td 69.369369 Tz (R-Rs ) Tj 1.891892 0 Td 67.267267 Tz (may ) Tj 1.4 0 Td 56.756757 Tz (be ) Tj 0.87027 0 Td 47.691441 Tz (selected ) Tj 2.459459 0 Td 47.297297 Tz (individually ) Tj 3.613514 0 Td 55.968468 Tz (from ) Tj 1.57027 0 Td 46.246246 Tz (the ) Tj 1.040541 0 Td 54.234234 Tz (group ) Tj 51.428571 0 0 51.428571 0 1433.39314 Tm 25.297222 0 Td 49.259259 Tz (consisting ) Tj 3.402778 0 Td 58.333333 Tz (of ) Tj 1.069444 0 Td 54.012346 Tz (hydrogen, ) Tj 3.363889 0 Td 51.446759 Tz (halogen, ) Tj 2.955556 0 Td 56.712963 Tz (C1-C1s ) Tj 2.527778 0 Td 44.290123 Tz (alkyl, ) Tj 2.080556 0 Td 57.253086 Tz (C1-C1s ) Tj 51.428571 0 0 51.428571 0 1390.910209 Tm 25.297222 0 Td 50 Tz (alkoxy, ) Tj 2.352778 0 Td 85.069444 Tz (C-Cs ) Tj 2.313889 0 Td 48.206019 Tz (alkenyl, ) Tj 2.566667 0 Td 85.069444 Tz (C-Cs ) Tj 2.352778 0 Td 50.05144 Tz (carboxyl, ) Tj 2.955556 0 Td 84.259259 Tz (C-Cs ) Tj 2.333333 0 Td 61.574074 Tz (carboxy ) Tj 51.428571 0 0 51.428571 0 1350.985612 Tm 25.297222 0 Td 44.830247 Tz (alkyl, ) Tj 1.808333 0 Td 85.87963 Tz (C-Cs ) Tj 2.275 0 Td 50.462963 Tz (alkoxy, ) Tj 2.333333 0 Td 84.259259 Tz (C-Cs ) Tj 2.275 0 Td 49.975634 Tz (halogen-substituted ) Tj 5.872222 0 Td 45.910494 Tz (alkyl, ) Tj 1.847222 0 Td 58.333333 Tz (any ) Tj 51.428571 0 0 51.428571 0 1306.77 Tm 25.277778 0 Td 60.493827 Tz (two ) Tj 1.283333 0 Td 56.712963 Tz (of ) Tj 0.797222 0 Td 55.092593 Tz (Such ) Tj 1.497222 0 Td 55.092593 Tz (groups ) Tj 2.177778 0 Td 56.388889 Tz (forms ) Tj 1.886111 0 Td 55.092593 Tz (a ) Tj 0.525 0 Td 49.583333 Tz (cycloalkyl ) Tj 3.188889 0 Td 44.074074 Tz (ring, ) Tj 1.497222 0 Td 58.333333 Tz (any ) Tj 1.225 0 Td 60.493827 Tz (two ) Tj 1.283333 0 Td 58.333333 Tz (of ) Tj 0.797222 0 Td 55.092593 Tz (Such ) Tj 51.428571 0 0 51.428571 0 1266.75092 Tm 25.297222 0 Td 54.552469 Tz (groups ) Tj 2.158333 0 Td 55.740741 Tz (forms ) Tj 1.847222 0 Td 56.712963 Tz (an ) Tj 0.855556 0 Td 49.151235 Tz (heterocyclic ) Tj 3.713889 0 Td 49.421296 Tz (ring ) Tj 1.341667 0 Td 52.5 Tz (\(such ) Tj 1.75 0 Td 50.231481 Tz (as ) Tj 0.797222 0 Td 50.411523 Tz (including ) Tj 2.897222 0 Td 55.092593 Tz (a ) Tj 0.525 0 Td 52.5 Tz (nitro ) Tj 51.428571 0 0 51.428571 0 1223.767038 Tm 25.297222 0 Td 57.253086 Tz (gen ) Tj 1.225 0 Td 60.763889 Tz (atom ) Tj 1.652778 0 Td 45.730453 Tz (therein\), ) Tj 2.683333 0 Td 48.611111 Tz (with, ) Tj 1.652778 0 Td 43.75 Tz (at ) Tj 0.738889 0 Td 44.722222 Tz (least ) Tj 1.536111 0 Td 58.333333 Tz (one ) Tj 1.205556 0 Td 57.037037 Tz (group ) Tj 1.925 0 Td 53.796296 Tz (being ) Tj 1.808333 0 Td 56.17284 Tz (something ) Tj 51.428571 0 0 51.428571 0 1182.525926 Tm 25.297222 0 Td 50.555556 Tz (other ) Tj 1.672222 0 Td 51.851852 Tz (than ) Tj 1.419444 0 Td 57.523148 Tz (hydrogen ) Tj 2.975 0 Td 52.662037 Tz (\(and ) Tj 1.458333 0 Td 48.611111 Tz (others ) Tj 1.944444 0 Td 50.231481 Tz (as ) Tj 0.797222 0 Td 51.851852 Tz (presented ) Tj 2.975 0 Td 57.037037 Tz (below ) Tj 1.944444 0 Td 59.953704 Tz (on ) Tj 0.894444 0 Td 57.523148 Tz (page ) Tj 51.428571 0 0 51.428571 0 1140.01868 Tm 25.355556 0 Td 44.560185 Tz (14\). ) Tj 1.205556 0 Td 66.435185 Tz (As ) Tj 0.991667 0 Td 53.148148 Tz (noted ) Tj 1.711111 0 Td 52.932099 Tz (above, ) Tj 2.041667 0 Td 49.907407 Tz (preferably ) Tj 3.208333 0 Td 72.916667 Tz (R. ) Tj 1.127778 0 Td 71.296296 Tz (R. ) Tj 1.030556 0 Td 58.333333 Tz (and ) Tj 1.244444 0 Td 56.712963 Tz (Rs ) Tj 0.875 0 Td 49.691358 Tz (are ) Tj 1.05 0 Td 53.652263 Tz (hydrogen, ) Tj 51.428571 0 0 51.428571 0 1098.350515 Tm 25.297222 0 Td 58.333333 Tz (and ) Tj 1.283333 0 Td 53.472222 Tz (R2 ) Tj 0.913889 0 Td 59.41358 Tz (and ) Tj 1.302778 0 Td 55.092593 Tz (Ra ) Tj 0.894444 0 Td 54.444444 Tz (being ) Tj 1.808333 0 Td 56.17284 Tz (any ) Tj 1.263889 0 Td 49.907407 Tz (other ) Tj 1.652778 0 Td 56.388889 Tz (group ) Tj 1.886111 0 Td 50.231481 Tz (as ) Tj 0.855556 0 Td 48.070988 Tz (noted. ) Tj 1.944444 0 Td 63.194444 Tz (Most ) Tj 1.672222 0 Td 55.092593 Tz (prefer ) Tj 52.857143 0 0 52.857143 0 1056.098266 Tm 24.613514 0 Td 50.45045 Tz (ably ) Tj 1.494595 0 Td 52.027027 Tz (only ) Tj 1.532432 0 Td 56.756757 Tz (one ) Tj 1.305405 0 Td 55.18018 Tz (of ) Tj 0.889189 0 Td 72.522523 Tz (R ) Tj 0.983784 0 Td 56.756757 Tz (and ) Tj 1.324324 0 Td 75.675676 Tz (R ) Tj 1.002703 0 Td 37.837838 Tz (is ) Tj 0.737838 0 Td 53.603604 Tz (any ) Tj 1.286486 0 Td 52.815315 Tz (such ) Tj 1.551351 0 Td 54.864865 Tz (group ) Tj 1.948649 0 Td 49.189189 Tz (other ) Tj 1.721622 0 Td 51.238739 Tz (than ) Tj 51.428571 0 0 51.428571 0 1014.994924 Tm 25.277778 0 Td 57.118056 Tz (hydrogen ) Tj 2.975 0 Td 48.611111 Tz (as ) Tj 0.875 0 Td 46.666667 Tz (well, ) Tj 1.613889 0 Td 60.493827 Tz (and ) Tj 1.302778 0 Td 35.648148 Tz (still ) Tj 1.361111 0 Td 61.574074 Tz (more ) Tj 1.672222 0 Td 49.907407 Tz (preferably ) Tj 3.247222 0 Td 55.092593 Tz (wherein ) Tj 2.547222 0 Td 55.092593 Tz (such ) Tj 1.575 0 Td 55.092593 Tz (a ) Tj 51.428571 0 0 51.428571 0 977.735346 Tm 25.297222 0 Td 56.388889 Tz (group ) Tj 1.905556 0 Td 37.268519 Tz (is ) Tj 0.622222 0 Td 58.333333 Tz (a ) Tj 0.505556 0 Td 55.092593 Tz (halogen ) Tj 2.527778 0 Td 50.231481 Tz (or ) Tj 0.758333 0 Td 55.092593 Tz (a ) Tj 0.486111 0 Td 46.720679 Tz (trihaloalkyl ) Tj 3.558333 0 Td 51.311728 Tz (group: ) Tj 31.428571 0 0 31.428571 0 799 Tm 41.681818 0 Td 106.060606 Tz (HOOC ) Tj 51.428571 0 0 51.428571 0 293.54 Tm 26.016667 0 Td 53.472222 Tz (This ) Tj 1.438889 0 Td 48.611111 Tz (inventive ) Tj 2.8 0 Td 59.953704 Tz (method ) Tj 2.275 0 Td 50.231481 Tz (thus ) Tj 1.380556 0 Td 53.06713 Tz (concerns ) Tj 2.702778 0 Td 49.691358 Tz (the ) Tj 1.011111 0 Td 48.935185 Tz (treatment, ) Tj 3.111111 0 Td 47.530864 Tz (via ) Tj 0.972222 0 Td 58.333333 Tz (any ) Tj 51.428571 0 0 51.428571 0 252.397129 Tm 25.297222 0 Td 48.251029 Tz (available ) Tj 2.761111 0 Td 54.62963 Tz (manner, ) Tj 2.45 0 Td 55.092593 Tz (Such ) Tj 1.477778 0 Td 48.611111 Tz (as ) Tj 0.758333 0 Td 48.881173 Tz (intravenous, ) Tj 3.694444 0 Td 46.180556 Tz (oral ) Tj 1.263889 0 Td 47.314815 Tz (ingestion, ) Tj 2.955556 0 Td 59.41358 Tz (and ) Tj 1.205556 0 Td 50.771605 Tz (the ) Tj 51.428571 0 0 51.428571 0 212.637786 Tm 25.297222 0 Td 42.12963 Tz (like, ) Tj 1.438889 0 Td 56.712963 Tz (of ) Tj 0.758333 0 Td 55.092593 Tz (a ) Tj 0.525 0 Td 62.654321 Tz (mammalian ) Tj 3.558333 0 Td 49.537037 Tz (Subject ) Tj 2.236111 0 Td 46.990741 Tz (to ) Tj 0.758333 0 Td 53.472222 Tz (reduce ) Tj 2.080556 0 Td 49.691358 Tz (autotaxin ) Tj 2.858333 0 Td 45.100309 Tz (availability ) Tj 51.428571 0 0 51.428571 0 170.252816 Tm 25.277778 0 Td 45.775463 Tz (therein. ) Tj 2.469444 0 Td 59.143519 Tz (Such ) Tj 1.633333 0 Td 58.333333 Tz (an ) Tj 0.952778 0 Td 48.611111 Tz (inventive ) Tj 2.877778 0 Td 59.953704 Tz (method ) Tj 2.411111 0 Td 66.975309 Tz (may ) Tj 1.419444 0 Td 48.611111 Tz (also ) Tj 1.419444 0 Td 58.693416 Tz (encompass ) Tj 3.402778 0 Td 49.691358 Tz (the ) Tj 1.428571 0 0 1.428571 0 885 Tm 974.4 0 Td 116.666667 Tz ( ) Tj ET Q endstream endobj 288 0 obj << /Length 1 >> stream q endstream endobj 289 0 obj << /Length 29600 >> stream Q q 0.24 0 0 0.24 0 0 cm BT /F1 1 Tf 3 Tr 62.857143 0 0 62.857143 0 3023 Tm 17.325 0 Td 83.522727 Tz (US ) Tj 1.240909 0 Td 57.154882 Tz (8,497,371 ) Tj 3.388636 0 Td 74.242424 Tz (B2 ) Tj 51.428571 0 0 51.428571 0 2914.02515 Tm 6.338889 0 Td 56.388889 Tz (broad ) Tj 1.827778 0 Td 51.131687 Tz (treatment ) Tj 2.877778 0 Td 58.333333 Tz (of ) Tj 0.777778 0 Td 49.691358 Tz (the ) Tj 1.069444 0 Td 61.574074 Tz (same ) Tj 1.613889 0 Td 49.537037 Tz (subject ) Tj 2.216667 0 Td 48.611111 Tz (for ) Tj 0.991667 0 Td 55.092593 Tz (a ) Tj 0.525 0 Td 61.574074 Tz (number ) Tj 2.313889 0 Td 58.333333 Tz (of ) Tj 0.777778 0 Td 46.450617 Tz (different ) Tj 51.428571 0 0 51.428571 0 2872.470886 Tm 6.358333 0 Td 53.877315 Tz (maladies ) Tj 2.936111 0 Td 49.907407 Tz (associated ) Tj 3.363889 0 Td 52.662037 Tz (with ) Tj 1.633333 0 Td 50.05144 Tz (autotaxin ) Tj 3.052778 0 Td 53.472222 Tz (presence ) Tj 2.897222 0 Td 59.41358 Tz (and ) Tj 1.419444 0 Td 45.37037 Tz (activity ) Tj 51.428571 0 0 51.428571 0 2829.090253 Tm 6.338889 0 Td 51.851852 Tz (within ) Tj 2.022222 0 Td 49.691358 Tz (the ) Tj 1.030556 0 Td 53.472222 Tz (subjects ) Tj 2.702778 0 Td 59.953704 Tz (body ) Tj 1.613889 0 Td 51.203704 Tz (\(such ) Tj 1.691667 0 Td 48.611111 Tz (as ) Tj 0.738889 0 Td 45.37037 Tz (to ) Tj 0.719444 0 Td 43.425926 Tz (treat ) Tj 1.4 0 Td 46.585648 Tz (obesity, ) Tj 2.372222 0 Td 53.148148 Tz (atheroscle ) Tj 51.428571 0 0 51.428571 0 2783.045278 Tm 6.358333 0 Td 43.209877 Tz (rosis, ) Tj 1.788889 0 Td 59.41358 Tz (and ) Tj 1.283333 0 Td 51.851852 Tz (the ) Tj 1.186111 0 Td 41.481481 Tz (like, ) Tj 1.477778 0 Td 50.231481 Tz (as ) Tj 0.894444 0 Td 53.148148 Tz (noted ) Tj 1.827778 0 Td 46.585648 Tz (herein\), ) Tj 2.488889 0 Td 48.070988 Tz (rather ) Tj 1.944444 0 Td 51.851852 Tz (than ) Tj 1.497222 0 Td 54.552469 Tz (simply ) Tj 2.255556 0 Td 47.530864 Tz (for ) Tj 51.428571 0 0 51.428571 0 2742.167095 Tm 6.358333 0 Td 53.472222 Tz (cancer ) Tj 2.275 0 Td 50.87963 Tz (treatments ) Tj 3.441667 0 Td 48.611111 Tz (alone. ) Tj 2.138889 0 Td 48.611111 Tz (Additionally, ) Tj 4.180556 0 Td 50.771605 Tz (the ) Tj 1.322222 0 Td 45.775463 Tz (specific ) Tj 2.605556 0 Td 83.179012 Tz (com ) Tj 51.428571 0 0 51.428571 0 2699.313823 Tm 6.358333 0 Td 58.333333 Tz (pounds ) Tj 2.275 0 Td 46.180556 Tz (that ) Tj 1.283333 0 Td 48.148148 Tz (exhibit ) Tj 2.177778 0 Td 49.074074 Tz (greater ) Tj 2.236111 0 Td 50.231481 Tz (than ) Tj 1.419444 0 Td 73.45679 Tz (50% ) Tj 1.536111 0 Td 52.256944 Tz (response ) Tj 2.683333 0 Td 46.990741 Tz (at ) Tj 0.7 0 Td 51.851852 Tz (a ) Tj 0.505556 0 Td 48.611111 Tz (single ) Tj 2.002778 0 Td 55.092593 Tz (10 ) Tj 51.428571 0 0 51.428571 0 2651 Tm 6.416667 0 Td 79.398148 Tz (uM ) Tj 1.127778 0 Td 55.092593 Tz (dose ) Tj 1.438889 0 Td 53.472222 Tz (and/or ) Tj 2.041667 0 Td 51.851852 Tz (a ) Tj 0.486111 0 Td 55.092593 Tz (K, ) Tj 0.797222 0 Td 59.953704 Tz (of ) Tj 0.797222 0 Td 44.560185 Tz (less ) Tj 1.244444 0 Td 51.041667 Tz (than ) Tj 1.419444 0 Td 58.333333 Tz (2 ) Tj 0.525 0 Td 81.018519 Tz (uM ) Tj 1.127778 0 Td 48.611111 Tz (for ) Tj 0.952778 0 Td 78.858025 Tz (ATX ) Tj 1.575 0 Td 46.990741 Tz (inhibition ) Tj 2.975 0 Td 50.771605 Tz (are ) Tj 51.428571 0 0 51.428571 0 2608.848939 Tm 6.338889 0 Td 51.851852 Tz (within ) Tj 2.119444 0 Td 48.611111 Tz (the ) Tj 1.108333 0 Td 55.092593 Tz (scope ) Tj 1.866667 0 Td 59.953704 Tz (of ) Tj 0.836111 0 Td 42.939815 Tz (this ) Tj 1.263889 0 Td 47.638889 Tz (invention. ) Tj 3.169444 0 Td 52.391975 Tz (Furthermore, ) Tj 3.986111 0 Td 55.902778 Tz (even ) Tj 1.575 0 Td 46.990741 Tz (if ) Tj 0.680556 0 Td 49.691358 Tz (the ) Tj 51.428571 0 0 51.428571 0 2567.647059 Tm 6.358333 0 Td 61.934156 Tz (compounds ) Tj 3.558333 0 Td 44.560185 Tz (that ) Tj 1.263889 0 Td 38.888889 Tz (fall ) Tj 1.127778 0 Td 50.771605 Tz (within ) Tj 2.041667 0 Td 48.611111 Tz (the ) Tj 1.069444 0 Td 55.092593 Tz (scope ) Tj 1.808333 0 Td 58.333333 Tz (of ) Tj 0.777778 0 Td 50.771605 Tz (the ) Tj 1.088889 0 Td 48.206019 Tz (reaction ) Tj 2.508333 0 Td 53.240741 Tz (product ) Tj 51.428571 0 0 51.428571 0 2521.955556 Tm 6.358333 0 Td 54.444444 Tz (noted ) Tj 1.808333 0 Td 57.037037 Tz (above ) Tj 1.905556 0 Td 58.333333 Tz (do ) Tj 0.933333 0 Td 50.771605 Tz (not ) Tj 1.088889 0 Td 48.148148 Tz (exhibit ) Tj 2.216667 0 Td 53.472222 Tz (such ) Tj 1.477778 0 Td 55.092593 Tz (a ) Tj 0.544444 0 Td 50.05144 Tz (threshold ) Tj 2.897222 0 Td 58.333333 Tz (improvement ) Tj 4.025 0 Td 50.231481 Tz (in ) Tj 51.428571 0 0 51.428571 0 2479.492754 Tm 6.358333 0 Td 78.858025 Tz (ATX ) Tj 1.594444 0 Td 45.075758 Tz (inhibition, ) Tj 3.15 0 Td 54.282407 Tz (such ) Tj 1.477778 0 Td 62.294239 Tz (compounds ) Tj 3.5 0 Td 49.691358 Tz (are ) Tj 1.05 0 Td 35.648148 Tz (still ) Tj 1.225 0 Td 50.771605 Tz (within ) Tj 2.022222 0 Td 49.691358 Tz (the ) Tj 1.05 0 Td 55.092593 Tz (scope ) Tj 1.788889 0 Td 58.333333 Tz (of ) Tj 51.428571 0 0 51.428571 0 2436.656566 Tm 6.338889 0 Td 44.560185 Tz (this ) Tj 1.302778 0 Td 50.05144 Tz (invention ) Tj 2.975 0 Td 46.450617 Tz (for ) Tj 1.05 0 Td 49.691358 Tz (the ) Tj 1.108333 0 Td 55.555556 Tz (purpose ) Tj 2.586111 0 Td 55.092593 Tz (of ) Tj 0.816667 0 Td 49.907407 Tz (providing, ) Tj 3.208333 0 Td 51.851852 Tz (as ) Tj 0.913889 0 Td 52.5 Tz (noted ) Tj 1.808333 0 Td 57.037037 Tz (previ ) Tj 51.428571 0 0 51.428571 0 2389.838095 Tm 6.358333 0 Td 47.530864 Tz (ously, ) Tj 1.925 0 Td 49.85755 Tz (intermediates ) Tj 4.102778 0 Td 47.530864 Tz (for ) Tj 1.011111 0 Td 48.148148 Tz (further ) Tj 2.216667 0 Td 50.231481 Tz (modification ) Tj 3.811111 0 Td 52.391975 Tz (and/or ) Tj 2.080556 0 Td 49.016204 Tz (reaction ) Tj 51.428571 0 0 51.428571 0 2347.927007 Tm 6.338889 0 Td 45.37037 Tz (to ) Tj 0.758333 0 Td 53.472222 Tz (optimize ) Tj 2.761111 0 Td 54.282407 Tz (such ) Tj 1.458333 0 Td 77.777778 Tz (ATX ) Tj 1.594444 0 Td 46.990741 Tz (inhibition ) Tj 3.033333 0 Td 42.12963 Tz (results. ) Tj 38.571429 0 0 38.571429 0 2248 Tm 10.992593 0 Td 90.740741 Tz (BRIEF ) Tj 3.007407 0 Td 94.668911 Tz (DESCRIPTION ) Tj 6.533333 0 Td 101.54321 Tz (OF ) Tj 1.451852 0 Td 105.144033 Tz (THE ) Tj 2.177778 0 Td 105.864198 Tz (DRAWINGS ) Tj 51.428571 0 0 51.428571 0 2143.67624 Tm 7.116667 0 Td 54.282407 Tz (FIG. ) Tj 1.536111 0 Td 48.611111 Tz (1 ) Tj 0.563889 0 Td 38.888889 Tz (is ) Tj 0.661111 0 Td 58.333333 Tz (a ) Tj 0.525 0 Td 50.411523 Tz (graphical ) Tj 2.916667 0 Td 49.074074 Tz (representation ) Tj 4.355556 0 Td 56.712963 Tz (of ) Tj 0.777778 0 Td 49.691358 Tz (the ) Tj 1.088889 0 Td 50.05144 Tz (autotaxin ) Tj 2.916667 0 Td 56.712963 Tz (inhi ) Tj 51.428571 0 0 51.428571 0 2100.435339 Tm 6.338889 0 Td 47.530864 Tz (bition ) Tj 1.886111 0 Td 47.962963 Tz (capability ) Tj 3.072222 0 Td 55.092593 Tz (of ) Tj 0.797222 0 Td 50.231481 Tz (lead ) Tj 1.380556 0 Td 64.00463 Tz (compound ) Tj 3.227778 0 Td 56.712963 Tz (A, ) Tj 0.855556 0 Td 51.851852 Tz (as ) Tj 0.797222 0 Td 51.446759 Tz (depicted ) Tj 2.644444 0 Td 52.391975 Tz (below. ) Tj 51.428571 0 0 51.428571 0 2044.923858 Tm 7.116667 0 Td 54.282407 Tz (FIG. ) Tj 1.477778 0 Td 58.333333 Tz (2 ) Tj 0.486111 0 Td 38.888889 Tz (is ) Tj 0.622222 0 Td 51.851852 Tz (a ) Tj 0.447222 0 Td 50.05144 Tz (graphical ) Tj 2.877778 0 Td 48.37963 Tz (representation ) Tj 4.219444 0 Td 55.092593 Tz (of ) Tj 0.738889 0 Td 49.691358 Tz (the ) Tj 1.069444 0 Td 44.398148 Tz (reactivity ) Tj 2.819444 0 Td 56.712963 Tz (of ) Tj 0.758333 0 Td 51.041667 Tz (lead ) Tj 51.428571 0 0 51.428571 0 1998.976501 Tm 6.358333 0 Td 64.00463 Tz (compound ) Tj 3.325 0 Td 58.333333 Tz (A, ) Tj 0.991667 0 Td 48.611111 Tz (as ) Tj 0.894444 0 Td 51.446759 Tz (depicted ) Tj 2.741667 0 Td 51.851852 Tz (below, ) Tj 2.177778 0 Td 46.990741 Tz (in ) Tj 0.836111 0 Td 54.444444 Tz (terms ) Tj 1.944444 0 Td 56.712963 Tz (of ) Tj 0.894444 0 Td 58.333333 Tz (Ki ) Tj 1.030556 0 Td 62.5 Tz (measure ) Tj 34.285714 0 0 34.285714 0 1961 Tm 9.625 0 Td 76.157407 Tz (mentS. ) Tj 51.428571 0 0 51.428571 0 1900.551171 Tm 7.116667 0 Td 59.62963 Tz (FIG.3 ) Tj 1.963889 0 Td 38.888889 Tz (is ) Tj 0.602778 0 Td 55.092593 Tz (a ) Tj 0.447222 0 Td 53.652263 Tz (histogram ) Tj 3.052778 0 Td 48.842593 Tz (representation ) Tj 4.258333 0 Td 53.472222 Tz (of ) Tj 0.719444 0 Td 49.691358 Tz (autotaxin ) Tj 2.838889 0 Td 47.638889 Tz (inhibition ) Tj 51.428571 0 0 51.428571 0 1858.561497 Tm 6.358333 0 Td 58.333333 Tz (of ) Tj 0.777778 0 Td 48.37963 Tz (representative ) Tj 4.258333 0 Td 48.611111 Tz (inventive ) Tj 2.8 0 Td 58.657407 Tz (compounds. ) Tj 51.428571 0 0 51.428571 0 1800.525593 Tm 7.116667 0 Td 54.282407 Tz (FIG. ) Tj 1.458333 0 Td 64.814815 Tz (4 ) Tj 0.544444 0 Td 38.888889 Tz (is ) Tj 0.641667 0 Td 55.092593 Tz (a ) Tj 0.447222 0 Td 50.411523 Tz (graphical ) Tj 2.877778 0 Td 49.305556 Tz (representation ) Tj 4.297222 0 Td 56.712963 Tz (of ) Tj 0.758333 0 Td 49.691358 Tz (autotaxin ) Tj 2.858333 0 Td 47.638889 Tz (inhibition ) Tj 51.428571 0 0 51.428571 0 1757.877743 Tm 6.358333 0 Td 45.37037 Tz (rates ) Tj 1.575 0 Td 47.530864 Tz (for ) Tj 1.011111 0 Td 48.37963 Tz (representative ) Tj 4.258333 0 Td 48.611111 Tz (inventive ) Tj 2.8 0 Td 58.333333 Tz (compounds. ) Tj 51.428571 0 0 51.428571 0 1702.074401 Tm 7.116667 0 Td 54.282407 Tz (FIG. ) Tj 1.438889 0 Td 61.574074 Tz (5 ) Tj 0.525 0 Td 38.888889 Tz (is ) Tj 0.602778 0 Td 58.333333 Tz (a ) Tj 0.447222 0 Td 54.012346 Tz (histogram ) Tj 3.091667 0 Td 48.611111 Tz (representation ) Tj 4.238889 0 Td 55.092593 Tz (of ) Tj 0.738889 0 Td 42.939815 Tz (cell ) Tj 1.205556 0 Td 51.49177 Tz (migration ) Tj 2.955556 0 Td 60.763889 Tz (char ) Tj 51.428571 0 0 51.428571 0 1655.119403 Tm 6.358333 0 Td 43.897306 Tz (acteristics ) Tj 3.227778 0 Td 46.759259 Tz (related ) Tj 2.236111 0 Td 46.990741 Tz (to ) Tj 0.894444 0 Td 46.296296 Tz (certain ) Tj 2.255556 0 Td 49.305556 Tz (representation ) Tj 4.433333 0 Td 48.971193 Tz (inventive ) Tj 2.936111 0 Td 82.098765 Tz (com ) Tj 51.428571 0 0 51.428571 0 1617 Tm 6.358333 0 Td 53.703704 Tz (pounds. ) Tj 38.571429 0 0 38.571429 0 1511 Tm 9.92963 0 Td 97.762346 Tz (DETAILED ) Tj 4.977778 0 Td 94.276094 Tz (DESCRIPTION ) Tj 6.533333 0 Td 99.382716 Tz (OF ) Tj 1.4 0 Td 106.584362 Tz (THE ) Tj 2.177778 0 Td 98.902606 Tz (INVENTION ) Tj 51.428571 0 0 51.428571 0 1405.261333 Tm 7.116667 0 Td 54.012346 Tz (Pipemidic ) Tj 3.111111 0 Td 51.041667 Tz (acid ) Tj 1.438889 0 Td 42.12963 Tz (itself ) Tj 1.613889 0 Td 54.012346 Tz (has ) Tj 1.186111 0 Td 56.712963 Tz (been ) Tj 1.594444 0 Td 55.092593 Tz (used ) Tj 1.516667 0 Td 45.37037 Tz (in ) Tj 0.738889 0 Td 50.771605 Tz (the ) Tj 1.088889 0 Td 50.231481 Tz (past ) Tj 1.4 0 Td 48.611111 Tz (as ) Tj 0.797222 0 Td 56.712963 Tz (an ) Tj 0.875 0 Td 55.902778 Tz (anti ) Tj 51.428571 0 0 51.428571 0 1358.859394 Tm 6.338889 0 Td 46.8107 Tz (bacterial ) Tj 2.819444 0 Td 64.00463 Tz (compound ) Tj 3.363889 0 Td 51.851852 Tz (\(quinolone-type ) Tj 4.958333 0 Td 45.664983 Tz (antibiotics ) Tj 3.325 0 Td 56.712963 Tz (have ) Tj 1.652778 0 Td 58.333333 Tz (been ) Tj 51.428571 0 0 51.428571 0 1310.078431 Tm 6.338889 0 Td 55.632716 Tz (widely ) Tj 2.158333 0 Td 55.902778 Tz (used ) Tj 1.497222 0 Td 47.530864 Tz (for ) Tj 1.011111 0 Td 49.691358 Tz (nearly ) Tj 1.925 0 Td 55.092593 Tz (a ) Tj 0.486111 0 Td 48.206019 Tz (century, ) Tj 2.508333 0 Td 43.75 Tz (in ) Tj 0.719444 0 Td 40.509259 Tz (fact\). ) Tj 1.672222 0 Td 49.200337 Tz (Derivatives ) Tj 3.422222 0 Td 55.092593 Tz (of ) Tj 0.777778 0 Td 55.902778 Tz (such ) Tj 51.428571 0 0 51.428571 0 1264.334928 Tm 6.358333 0 Td 55.092593 Tz (a ) Tj 0.466667 0 Td 55.092593 Tz (base ) Tj 1.477778 0 Td 64.00463 Tz (compound ) Tj 3.188889 0 Td 57.523148 Tz (have ) Tj 1.536111 0 Td 56.712963 Tz (been ) Tj 1.536111 0 Td 55.092593 Tz (developed ) Tj 3.111111 0 Td 48.611111 Tz (as ) Tj 0.777778 0 Td 57.523148 Tz (improved ) Tj 2.897222 0 Td 51.446759 Tz (antibiot ) Tj 51.428571 0 0 51.428571 0 1215.583234 Tm 6.358333 0 Td 44.290123 Tz (ics ) Tj 0.913889 0 Td 51.851852 Tz (as ) Tj 0.777778 0 Td 51.041667 Tz (well ) Tj 1.341667 0 Td 53.703704 Tz (through ) Tj 2.372222 0 Td 50.771605 Tz (the ) Tj 1.030556 0 Td 46.990741 Tz (years. ) Tj 1.886111 0 Td 56.712963 Tz (However, ) Tj 2.858333 0 Td 55.092593 Tz (such ) Tj 1.477778 0 Td 61.574074 Tz (compounds ) Tj 3.461111 0 Td 56.712963 Tz (have ) Tj 51.428571 0 0 51.428571 0 1165.447527 Tm 6.358333 0 Td 52.256944 Tz (involved ) Tj 2.663889 0 Td 49.691358 Tz (the ) Tj 1.088889 0 Td 50.771605 Tz (modification ) Tj 3.830556 0 Td 58.333333 Tz (of ) Tj 0.777778 0 Td 49.691358 Tz (the ) Tj 1.069444 0 Td 48.070988 Tz (actual ) Tj 1.925 0 Td 54.012346 Tz (pipemidic ) Tj 3.111111 0 Td 50.231481 Tz (acid ) Tj 1.380556 0 Td 67.24537 Tz (back ) Tj 51.428571 0 0 51.428571 0 1120.168153 Tm 6.338889 0 Td 59.953704 Tz (bone ) Tj 1.691667 0 Td 51.851852 Tz (\(Such ) Tj 1.808333 0 Td 46.990741 Tz (as ) Tj 0.836111 0 Td 50.411523 Tz (replacing ) Tj 2.936111 0 Td 56.712963 Tz (an ) Tj 0.933333 0 Td 55.092593 Tz (aza ) Tj 1.205556 0 Td 56.388889 Tz (group ) Tj 1.963889 0 Td 57.523148 Tz (from ) Tj 1.613889 0 Td 58.333333 Tz (an ) Tj 0.952778 0 Td 49.151235 Tz (heterocyclic ) Tj 51.428571 0 0 51.428571 0 1071.188406 Tm 6.358333 0 Td 48.611111 Tz (constituent ) Tj 3.383333 0 Td 53.472222 Tz (with ) Tj 1.477778 0 Td 58.333333 Tz (a ) Tj 0.563889 0 Td 51.58179 Tz (methyltluoro ) Tj 3.927778 0 Td 46.180556 Tz (Substiluent, ) Tj 3.538889 0 Td 51.851852 Tz (or ) Tj 0.797222 0 Td 50.05144 Tz (replacing ) Tj 2.897222 0 Td 49.691358 Tz (the ) Tj 51.428571 0 0 51.428571 0 1027.848485 Tm 6.358333 0 Td 52.314815 Tz (N-cthyl ) Tj 2.488889 0 Td 56.388889 Tz (group ) Tj 2.002778 0 Td 52.662037 Tz (with ) Tj 1.555556 0 Td 55.092593 Tz (a ) Tj 0.622222 0 Td 53.596866 Tz (N-cyclopropyl ) Tj 4.511111 0 Td 50.925926 Tz (moiety, ) Tj 2.391667 0 Td 51.851852 Tz (as ) Tj 0.913889 0 Td 55.092593 Tz (examples\) ) Tj 51.428571 0 0 51.428571 0 976.393365 Tm 6.358333 0 Td 48.070988 Tz (rather ) Tj 1.808333 0 Td 52.662037 Tz (than ) Tj 1.4 0 Td 49.016204 Tz (reacting ) Tj 2.45 0 Td 50.771605 Tz (the ) Tj 1.030556 0 Td 54.012346 Tz (pipemidic ) Tj 3.052778 0 Td 51.041667 Tz (acid ) Tj 1.361111 0 Td 52.662037 Tz (with ) Tj 1.380556 0 Td 58.333333 Tz (an ) Tj 0.816667 0 Td 49.016204 Tz (additive ) Tj 2.469444 0 Td 56.388889 Tz (group ) Tj 51.428571 0 0 51.428571 0 927.815366 Tm 6.358333 0 Td 58.333333 Tz (and ) Tj 1.244444 0 Td 48.251029 Tz (retaining ) Tj 2.8 0 Td 49.691358 Tz (the ) Tj 1.069444 0 Td 54.012346 Tz (pipemidic ) Tj 3.130556 0 Td 51.041667 Tz (acid ) Tj 1.4 0 Td 58.333333 Tz (backbone ) Tj 3.013889 0 Td 45.37037 Tz (in ) Tj 0.758333 0 Td 42.777778 Tz (total ) Tj 1.497222 0 Td 50.555556 Tz (\(save ) Tj 1.730556 0 Td 47.530864 Tz (for ) Tj 51.428571 0 0 51.428571 0 881.489209 Tm 6.338889 0 Td 50.771605 Tz (the ) Tj 1.108333 0 Td 47.395833 Tz (reactive ) Tj 2.430556 0 Td 57.118056 Tz (hydrogen ) Tj 2.916667 0 Td 51.041667 Tz (attached ) Tj 2.605556 0 Td 48.611111 Tz (to ) Tj 0.777778 0 Td 49.691358 Tz (the ) Tj 1.05 0 Td 49.421296 Tz (heterocyclic ) Tj 3.772222 0 Td 46.666667 Tz (nitrogen\). ) Tj 51.428571 0 0 51.428571 0 832.092683 Tm 6.358333 0 Td 66.435185 Tz (As ) Tj 1.011111 0 Td 49.907407 Tz (such, ) Tj 1.672222 0 Td 53.06713 Tz (although ) Tj 2.741667 0 Td 45.868946 Tz (antibacterial ) Tj 3.772222 0 Td 45.37037 Tz (effects ) Tj 2.119444 0 Td 68.055556 Tz (may ) Tj 1.419444 0 Td 58.333333 Tz (be ) Tj 0.875 0 Td 49.826389 Tz (possible ) Tj 2.586111 0 Td 54.282407 Tz (with ) Tj 51.428571 0 0 51.428571 0 784.990566 Tm 6.338889 0 Td 50.771605 Tz (the ) Tj 1.030556 0 Td 45.775463 Tz (specific ) Tj 2.333333 0 Td 61.574074 Tz (compounds ) Tj 3.480556 0 Td 51.851852 Tz (of ) Tj 0.7 0 Td 43.75 Tz (this ) Tj 1.186111 0 Td 47.962963 Tz (invention, ) Tj 2.975 0 Td 50.05144 Tz (primarily ) Tj 2.858333 0 Td 54.282407 Tz (Such ) Tj 1.419444 0 Td 83.179012 Tz (com ) Tj 51.428571 0 0 51.428571 0 738.240385 Tm 6.358333 0 Td 58.333333 Tz (pounds ) Tj 2.236111 0 Td 48.611111 Tz (exhibit ) Tj 2.177778 0 Td 50.771605 Tz (the ) Tj 1.05 0 Td 46.450617 Tz (target ) Tj 1.808333 0 Td 47.395833 Tz (efficacy ) Tj 2.469444 0 Td 43.75 Tz (in ) Tj 0.7 0 Td 52.662037 Tz (reducing ) Tj 2.702778 0 Td 50.05144 Tz (autotaxin ) Tj 2.897222 0 Td 59.143519 Tz (reac ) Tj 51.428571 0 0 51.428571 0 686.780247 Tm 6.338889 0 Td 42.669753 Tz (tivity ) Tj 1.711111 0 Td 48.611111 Tz (for ) Tj 1.030556 0 Td 48.611111 Tz (the ) Tj 1.05 0 Td 52.5 Tz (conversion ) Tj 3.305556 0 Td 58.333333 Tz (of ) Tj 0.777778 0 Td 74.537037 Tz (LPC ) Tj 1.516667 0 Td 45.37037 Tz (to ) Tj 0.777778 0 Td 59.143519 Tz (LPA. ) Tj 1.575 0 Td 65.895062 Tz (The ) Tj 1.341667 0 Td 47.530864 Tz (retention ) Tj 2.741667 0 Td 56.712963 Tz (of ) Tj 0.797222 0 Td 48.611111 Tz (the ) Tj 51.428571 0 0 51.428571 0 640.727932 Tm 6.358333 0 Td 53.652263 Tz (pipemidic ) Tj 3.052778 0 Td 51.851852 Tz (acid ) Tj 1.380556 0 Td 58.738426 Tz (backbone ) Tj 2.975 0 Td 45.37037 Tz (at ) Tj 0.680556 0 Td 43.75 Tz (this ) Tj 1.205556 0 Td 51.203704 Tz (point ) Tj 1.672222 0 Td 50.231481 Tz (thus ) Tj 1.380556 0 Td 57.407407 Tz (eschews ) Tj 2.566667 0 Td 58.333333 Tz (any ) Tj 1.225 0 Td 55.092593 Tz (rela ) Tj 51.428571 0 0 51.428571 0 593.166667 Tm 6.338889 0 Td 47.800926 Tz (tion ) Tj 1.302778 0 Td 46.990741 Tz (to ) Tj 0.738889 0 Td 50.771605 Tz (the ) Tj 1.05 0 Td 46.018519 Tz (antibiotic ) Tj 2.975 0 Td 61.574074 Tz (compounds ) Tj 3.519444 0 Td 56.712963 Tz (of ) Tj 0.758333 0 Td 49.691358 Tz (the ) Tj 1.05 0 Td 45.37037 Tz (past; ) Tj 1.555556 0 Td 55.092593 Tz (a ) Tj 0.505556 0 Td 47.800926 Tz (reactant ) Tj 2.430556 0 Td 66.435185 Tz (prod ) Tj 51.428571 0 0 51.428571 0 544.935252 Tm 6.338889 0 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61.574074 Tz (compounds ) Tj 3.752778 0 Td 59.143519 Tz (were ) Tj 1.827778 0 Td 45.37037 Tz (in ) Tj 0.972222 0 Td 52.777778 Tz (essence ) Tj 2.644444 0 Td 55.092593 Tz (developed ) Tj 51.428571 0 0 51.428571 0 344.123649 Tm 6.338889 0 Td 54.166667 Tz (through ) Tj 2.411111 0 Td 49.691358 Tz (the ) Tj 1.030556 0 Td 45.959596 Tz (realization ) Tj 3.188889 0 Td 45.37037 Tz (that ) Tj 1.205556 0 Td 51.851852 Tz (a ) Tj 0.466667 0 Td 36.944444 Tz (first ) Tj 1.263889 0 Td 51.851852 Tz (small ) Tj 1.730556 0 Td 54.6875 Tz (molecule ) Tj 2.722222 0 Td 77.777778 Tz (ATX ) Tj 1.555556 0 Td 52.932099 Tz (inhibi ) Tj 51.428571 0 0 51.428571 0 302.29867 Tm 6.338889 0 Td 40.509259 Tz (tor, ) Tj 1.166667 0 Td 52.5 Tz (noted ) Tj 1.691667 0 Td 57.685185 Tz (below ) Tj 1.925 0 Td 51.851852 Tz (as ) Tj 0.758333 0 Td 64.00463 Tz (compound ) Tj 3.188889 0 Td 84.259259 Tz (A ) Tj 0.622222 0 Td 50.411523 Tz (exhibited ) Tj 2.858333 0 Td 53.472222 Tz (high ) Tj 1.419444 0 Td 47.395833 Tz (efficacy ) Tj 2.430556 0 Td 48.611111 Tz (as ) Tj 0.719444 0 Td 61.574074 Tz (an ) Tj 51.428571 0 0 51.428571 0 257.595934 Tm 6.358333 0 Td 50.05144 Tz (autotaxin ) Tj 3.013889 0 Td 43.75 Tz (inhibitor. ) Tj 2.916667 0 Td 66.435185 Tz (As ) Tj 1.127778 0 Td 48.070988 Tz (noted. ) Tj 2.080556 0 Td 55.092593 Tz (Such ) Tj 1.613889 0 Td 58.333333 Tz (a ) Tj 0.661111 0 Td 63.599537 Tz (compound ) Tj 3.363889 0 Td 50.411523 Tz (exhibited ) Tj 51.428571 0 0 51.428571 0 215.362745 Tm 6.358333 0 Td 46.450617 Tz (effective ) Tj 2.702778 0 Td 52.256944 Tz (response ) Tj 2.644444 0 Td 46.990741 Tz (to ) Tj 0.719444 0 Td 50.05144 Tz (autotaxin ) Tj 2.877778 0 Td 44.560185 Tz (activity ) Tj 2.333333 0 Td 56.17284 Tz (\(Graph ) Tj 2.255556 0 Td 56.712963 Tz (B\) ) Tj 0.816667 0 Td 51.851852 Tz (\(FIG. ) Tj 1.769444 0 Td 48.611111 Tz (1\) ) Tj 0.738889 0 Td 50.231481 Tz (as ) Tj 51.428571 0 0 51.428571 0 169.042184 Tm 6.338889 0 Td 52.662037 Tz (well ) Tj 1.438889 0 Td 50.231481 Tz (as ) Tj 0.836111 0 Td 51.851852 Tz (K, ) Tj 0.816667 0 Td 43.75 Tz (at ) Tj 0.738889 0 Td 56.064815 Tz (micromolar ) Tj 3.519444 0 Td 50.462963 Tz (concentrations ) Tj 4.433333 0 Td 56.712963 Tz (\(Graph ) Tj 2.216667 0 Td 61.574074 Tz (C\) ) Tj 0.933333 0 Td 51.203704 Tz (\(FIG. ) Tj 1.769444 0 Td 41.049383 Tz (2\): ) Tj 30 0 0 30 0 2547 Tm 41.666667 0 Td 75 Tz (10 ) Tj 30 0 0 30 0 2339 Tm 41.666667 0 Td 63.888889 Tz (15 ) Tj 30 0 0 30 0 1923 Tm 41.6 0 Td 77.777778 Tz (25 ) Tj 30 0 0 30 0 1716 Tm 41.6 0 Td 80.555556 Tz (30 ) Tj 30 0 0 30 0 1507 Tm 41.6 0 Td 77.777778 Tz (35 ) Tj 30 0 0 30 0 1299 Tm 41.566667 0 Td 83.333333 Tz (40 ) Tj 30 0 0 30 0 1091 Tm 41.566667 0 Td 80.555556 Tz (45 ) Tj 30 0 0 30 0 883 Tm 41.6 0 Td 80.555556 Tz (50 ) Tj 30 0 0 30 0 675 Tm 41.6 0 Td 77.777778 Tz (55 ) Tj 30 0 0 30 0 467 Tm 41.633333 0 Td 77.777778 Tz (60 ) Tj 30 0 0 30 0 259 Tm 41.633333 0 Td 75 Tz (65 ) Tj 52.857143 0 0 52.857143 0 2968 Tm 32.672973 0 Td 74.099099 Tz (10 ) Tj 31.428571 0 0 31.428571 0 2254 Tm 64.75 0 Td 111.363636 Tz (C ) Tj 51.428571 0 0 51.428571 0 2072.628866 Tm 26.016667 0 Td 66.435185 Tz (As ) Tj 0.991667 0 Td 38.888889 Tz (is ) Tj 0.661111 0 Td 47.800926 Tz (evident, ) Tj 2.45 0 Td 44.560185 Tz (this ) Tj 1.263889 0 Td 50.231481 Tz (lead ) Tj 1.380556 0 Td 64.00463 Tz (compound ) Tj 3.227778 0 Td 84.259259 Tz (A ) Tj 0.661111 0 Td 44.290123 Tz (\(at ) Tj 1.030556 0 Td 101.54321 Tz (10M ) Tj 2.022222 0 Td 56.532922 Tz (concentra ) Tj 51.428571 0 0 51.428571 0 2031.145299 Tm 25.277778 0 Td 46.666667 Tz (tion\) ) Tj 1.672222 0 Td 53.796296 Tz (completely ) Tj 3.519444 0 Td 55.092593 Tz (blocked ) Tj 2.586111 0 Td 59.953704 Tz (ATX-mediated ) Tj 4.588889 0 Td 50.555556 Tz (hydrolysis ) Tj 3.325 0 Td 59.953704 Tz (of ) Tj 0.894444 0 Td 50.771605 Tz (the ) Tj 51.428571 0 0 51.428571 0 1989.116645 Tm 25.316667 0 Td 47.890947 Tz (synthetic ) Tj 2.936111 0 Td 72.106481 Tz (FRET ) Tj 2.061111 0 Td 50.925926 Tz (reagent ) Tj 2.430556 0 Td 57.523148 Tz (FS-3 ) Tj 1.691667 0 Td 45.37037 Tz (\(1 ) Tj 0.952778 0 Td 57.523148 Tz (uM\), ) Tj 1.691667 0 Td 51.851852 Tz (a ) Tj 0.622222 0 Td 51.311728 Tz (highly ) Tj 2.138889 0 Td 48.611111 Tz (surprising ) Tj 48.571429 0 0 48.571429 0 1942 Tm 26.785294 0 Td 44.607843 Tz (result. ) Tj 2.141176 0 Td 66.053922 Tz (From ) Tj 1.811765 0 Td 45.465686 Tz (this ) Tj 1.317647 0 Td 47.46732 Tz (realization, ) Tj 3.623529 0 Td 36.029412 Tz (it ) Tj 0.617647 0 Td 64.052288 Tz (was ) Tj 1.379412 0 Td 54.044118 Tz (then ) Tj 1.502941 0 Td 57.647059 Tz (determined ) Tj 3.664706 0 Td 48.039216 Tz (that ) Tj 1.317647 0 Td 46.323529 Tz (this ) Tj 51.428571 0 0 51.428571 0 1898.570186 Tm 25.297222 0 Td 40.277778 Tz (initial ) Tj 1.944444 0 Td 64.00463 Tz (compound ) Tj 3.325 0 Td 47.530864 Tz (inhibited ) Tj 2.780556 0 Td 78.858025 Tz (ATX ) Tj 1.691667 0 Td 46.450617 Tz (via ) Tj 1.108333 0 Td 51.851852 Tz (a ) Tj 0.602778 0 Td 60.601852 Tz (mixed-mode ) Tj 3.888889 0 Td 70.648148 Tz (mecha ) Tj 51.428571 0 0 51.428571 0 1853 Tm 25.297222 0 Td 58.333333 Tz (nism ) Tj 1.536111 0 Td 54.282407 Tz (with ) Tj 1.4 0 Td 56.712963 Tz (an ) Tj 0.855556 0 Td 52.932099 Tz (ICs ) Tj 1.361111 0 Td 58.333333 Tz (of ) Tj 0.777778 0 Td 51.388889 Tz (1.6+0.4 ) Tj 2.352778 0 Td 70.648148 Tz (uMand ) Tj 2.255556 0 Td 53.472222 Tz (K, ) Tj 0.777778 0 Td 58.333333 Tz (of ) Tj 0.777778 0 Td 46.450617 Tz (1.6 ) Tj 1.011111 0 Td 62.654321 Tz (uM. ) Tj 1.263889 0 Td 59.953704 Tz (Such ) Tj 1.555556 0 Td 55.092593 Tz (a ) Tj 0.466667 0 Td 59.41358 Tz (low ) Tj 51.428571 0 0 51.428571 0 1811.895238 Tm 25.297222 0 Td 57.037037 Tz (micromolar ) Tj 3.597222 0 Td 47.170782 Tz (inhibitor ) Tj 2.741667 0 Td 50.231481 Tz (lead ) Tj 1.380556 0 Td 64.409722 Tz (compound ) Tj 3.305556 0 Td 51.041667 Tz (then ) Tj 1.438889 0 Td 52.211934 Tz (permitted ) Tj 3.013889 0 Td 48.148148 Tz (further ) Tj 51.428571 0 0 51.428571 0 1769.882641 Tm 25.297222 0 Td 50.231481 Tz (research ) Tj 2.683333 0 Td 46.990741 Tz (into ) Tj 1.361111 0 Td 46.8107 Tz (potential ) Tj 2.8 0 Td 45.58642 Tz (diversification ) Tj 4.375 0 Td 45.37037 Tz (strategies ) Tj 2.975 0 Td 45.37037 Tz (to ) Tj 0.816667 0 Td 51.446759 Tz (generate ) Tj 51.428571 0 0 51.428571 0 1728.151899 Tm 25.316667 0 Td 46.8107 Tz (structure ) Tj 2.8 0 Td 45.37037 Tz (activity ) Tj 2.508333 0 Td 47.260802 Tz (relationship ) Tj 3.733333 0 Td 62.87037 Tz (\(SAR\) ) Tj 2.177778 0 Td 50.231481 Tz (data ) Tj 1.516667 0 Td 48.611111 Tz (for ) Tj 1.147222 0 Td 49.691358 Tz (the ) Tj 1.186111 0 Td 49.826389 Tz (possible ) Tj 51.428571 0 0 51.428571 0 1686.613527 Tm 25.297222 0 Td 45.601852 Tz (identification ) Tj 4.025 0 Td 56.712963 Tz (of ) Tj 0.777778 0 Td 61.574074 Tz (more ) Tj 1.633333 0 Td 50.771605 Tz (potent ) Tj 1.983333 0 Td 54.012346 Tz (analog ) Tj 2.119444 0 Td 58.333333 Tz (compounds. ) Tj 3.733333 0 Td 34.027778 Tz (It ) Tj 0.563889 0 Td 61.574074 Tz (was ) Tj 1.302778 0 Td 55.092593 Tz (real ) Tj 52.857143 0 0 52.857143 0 1642.363412 Tm 24.613514 0 Td 44.774775 Tz (ized, ) Tj 1.532432 0 Td 50.45045 Tz (as ) Tj 0.794595 0 Td 52.027027 Tz (provided ) Tj 2.705405 0 Td 44.144144 Tz (in ) Tj 0.7 0 Td 48.198198 Tz (greater ) Tj 2.175676 0 Td 43.618619 Tz (detail ) Tj 1.759459 0 Td 50.975976 Tz (below, ) Tj 2.043243 0 Td 44.144144 Tz (that ) Tj 1.248649 0 Td 48.348348 Tz (the ) Tj 1.059459 0 Td 49.504505 Tz (derivatiza ) Tj 51.428571 0 0 51.428571 0 1601.69153 Tm 25.277778 0 Td 46.990741 Tz (tion ) Tj 1.438889 0 Td 55.092593 Tz (of ) Tj 0.816667 0 Td 54.012346 Tz (pipemidic ) Tj 3.169444 0 Td 51.851852 Tz (acid ) Tj 1.516667 0 Td 52.662037 Tz (with ) Tj 1.555556 0 Td 49.768519 Tz (isothiocyanate ) Tj 4.452778 0 Td 47.170782 Tz (reactants ) Tj 2.838889 0 Td 61.574074 Tz (was ) Tj 1.380556 0 Td 55.092593 Tz (a ) Tj 51.428571 0 0 51.428571 0 1561.459827 Tm 25.277778 0 Td 51.851852 Tz (highly ) Tj 2.061111 0 Td 46.8107 Tz (effective ) Tj 2.722222 0 Td 49.259259 Tz (route ) Tj 1.652778 0 Td 46.990741 Tz (to ) Tj 0.777778 0 Td 55.092593 Tz (a ) Tj 0.525 0 Td 53.796296 Tz (range ) Tj 1.808333 0 Td 56.712963 Tz (of ) Tj 0.797222 0 Td 52.314815 Tz (analogs ) Tj 2.411111 0 Td 58.333333 Tz (of ) Tj 0.777778 0 Td 64.409722 Tz (compound ) Tj 3.247222 0 Td 56.712963 Tz (A. ) Tj 51.428571 0 0 51.428571 0 1518.415617 Tm 25.297222 0 Td 57.685185 Tz (above ) Tj 2.041667 0 Td 52.314815 Tz (bearing ) Tj 2.547222 0 Td 50 Tz (various ) Tj 2.45 0 Td 47.530864 Tz (Substituents ) Tj 3.791667 0 Td 58.333333 Tz (on ) Tj 1.05 0 Td 49.691358 Tz (the ) Tj 1.205556 0 Td 52.314815 Tz (phenylthiourea ) Tj 51.428571 0 0 51.428571 0 1477.776952 Tm 25.297222 0 Td 48.070988 Tz (motif. ) Tj 1.944444 0 Td 64.814815 Tz (As ) Tj 0.972222 0 Td 53.877315 Tz (provided ) Tj 2.761111 0 Td 52.932099 Tz (below, ) Tj 2.1 0 Td 56.712963 Tz (an ) Tj 0.894444 0 Td 49.259259 Tz (array ) Tj 1.691667 0 Td 58.333333 Tz (of ) Tj 0.797222 0 Td 61.934156 Tz (compounds ) Tj 3.577778 0 Td 57.523148 Tz (were ) Tj 1.613889 0 Td 61.574074 Tz (cre ) Tj 51.428571 0 0 51.428571 0 1434.526316 Tm 25.297222 0 Td 51.041667 Tz 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1.327358 0 Td 72.641509 Tz (/ ) Tj 4.279245 0 Td 57.45283 Tz (nisms ) Tj 1.961321 0 Td 48.427673 Tz (for ) Tj 1.030189 0 Td 56.132075 Tz (a ) Tj 0.59434 0 Td 45.235849 Tz (relatively ) Tj 2.932075 0 Td 52.830189 Tz (small ) Tj 1.80283 0 Td 52.169811 Tz (proportion ) Tj 3.348113 0 Td 61.084906 Tz (of ) Tj 0.832075 0 Td 50.628931 Tz (the ) Tj 1.109434 0 Td 66.037736 Tz (known ) Tj 2.218868 0 Td 54.481132 Tz (inhibi ) Tj 50.15873 0 0 50.15873 0 2000.717073 Tm 15.211709 0 Td 79.746835 Tz (NN ) Tj 6.020886 0 Td 76.424051 Tz (N ) Tj 4.685127 0 Td 43.196203 Tz (tors. ) Tj 1.854114 0 Td 47.515823 Tz (Inhibitors ) Tj 3.389241 0 Td 53.164557 Tz (with ) Tj 1.814241 0 Td 51.503165 Tz (reported ) Tj 2.97057 0 Td 62.763713 Tz (mechanism ) Tj 3.867722 0 Td 61.471519 Tz (of ) Tj 1.136392 0 Td 48.512658 Tz (inhibition ) Tj 61.587302 0 0 61.587302 0 1957.958333 Tm 11.625773 0 Td 86.597938 Tz (W ) Tj 1.380155 0 Td 94.716495 Tz (f ) Tj 8.118557 0 Td 42.912371 Tz (include ) Tj 2.013402 0 Td 38.78866 Tz (L-histidine, ) Tj 3.020103 0 Td 58.634021 Tz (LPA ) Tj 1.250258 0 Td 49.613402 Tz (and ) Tj 1.087887 0 Td 42.622423 Tz (S1P, ) Tj 1.282732 0 Td 47.597029 Tz (FTY720-phosphate, ) Tj 5.033505 0 Td 50.515464 Tz (and ) Tj 51.428571 0 0 51.428571 0 1916.305925 Tm 24.266667 0 Td 45.37037 Tz (25 ) Tj 1.069444 0 Td 48.611111 Tz (non-lipid ) Tj 2.994444 0 Td 51.851852 Tz (Small ) Tj 1.925 0 Td 51.527778 Tz (molecules. ) Tj 3.5 0 Td 47.727273 Tz (L-histidine ) Tj 3.5 0 Td 52.932099 Tz (demonstrates ) Tj 4.2 0 Td 72.376543 Tz (non ) Tj 48.928571 0 0 48.928571 0 1875.726291 Tm 24.668613 0 Td 64.720195 Tz (C ) Tj 1.921168 0 Td 54.191551 Tz (competitive ) Tj 3.862774 0 Td 47.378898 Tz (inhibition. ) Tj 3.474453 0 Td 73.803731 Tz (LPA ) Tj 1.573723 0 Td 62.449311 Tz (and ) Tj 1.389781 0 Td 69.261963 Tz (S1P ) Tj 1.532847 0 Td 57.055961 Tz (demonstrated ) Tj 4.394161 0 Td 70.851582 Tz (mixed ) Tj 51.428571 0 0 51.428571 0 1833.016352 Tm 25.297222 0 Td 67.24537 Tz (mode ) Tj 1.788889 0 Td 46.342593 Tz (inhibition ) Tj 2.975 0 Td 52.662037 Tz (with ) Tj 1.458333 0 Td 70.216049 Tz (LPA ) Tj 1.419444 0 Td 54.552469 Tz (having ) Tj 2.1 0 Td 48.611111 Tz (a ) Tj 0.486111 0 Td 53.472222 Tz (K, ) Tj 0.797222 0 Td 59.953704 Tz (of ) Tj 0.797222 0 Td 50.231481 Tz (-0.1 ) Tj 1.497222 0 Td 62.654321 Tz (uM, ) Tj 1.263889 0 Td 59.41358 Tz (and ) Tj 1.205556 0 Td 34.027778 Tz (it ) Tj 0.563889 0 Td 61.574074 Tz (was ) Tj 51.428571 0 0 51.428571 0 1795.139303 Tm 25.297222 0 Td 50.636574 Tz (reported ) Tj 2.702778 0 Td 44.560185 Tz (that ) Tj 1.341667 0 Td 58.940972 Tz (FTY720-phosphate ) Tj 5.911111 0 Td 47.530864 Tz (inhibited ) Tj 2.8 0 Td 77.777778 Tz (ATX ) Tj 1.672222 0 Td 45.37037 Tz (in ) Tj 0.816667 0 Td 49.691358 Tz (the ) Tj 1.147222 0 Td 59.41358 Tz (low ) Tj 51.428571 0 0 51.428571 0 1751.839952 Tm 25.297222 0 Td 51.527778 Tz (millimolar ) Tj 3.208333 0 Td 53.796296 Tz (range ) Tj 1.691667 0 Td 59.953704 Tz (by ) Tj 0.875 0 Td 55.092593 Tz (a ) Tj 0.447222 0 Td 51.557239 Tz (competitive ) Tj 3.558333 0 Td 60.133745 Tz (mechanism ) Tj 3.422222 0 Td 51.851852 Tz (with ) Tj 1.361111 0 Td 58.333333 Tz (a ) Tj 0.505556 0 Td 51.851852 Tz (K, ) Tj 0.777778 0 Td 53.472222 Tz (of ) Tj 0.719444 0 Td 49.691358 Tz (0.2 ) Tj 50.43956 0 0 50.43956 0 1709.396896 Tm 17.664706 0 Td 59.477124 Tz (CF ) Tj 7.077778 0 Td 46.259985 Tz (30 ) Tj 1.090414 0 Td 63.882837 Tz (uM. ) Tj 1.24902 0 Td 69.389978 Tz (As ) Tj 0.951634 0 Td 48.242556 Tz (well, ) Tj 1.586057 0 Td 33.042847 Tz (it ) Tj 0.495643 0 Td 55.071411 Tz (has ) Tj 1.11024 0 Td 58.651053 Tz (been ) Tj 1.506754 0 Td 51.399984 Tz (disclosed ) Tj 2.874728 0 Td 47.086057 Tz (that ) Tj 1.229194 0 Td 48.148148 Tz (certain ) Tj 2.180828 0 Td 47.581699 Tz (non-lipid, ) Tj 2.973856 0 Td 53.529412 Tz (small ) Tj 51.428571 0 0 51.428571 0 1669.002469 Tm 25.297222 0 Td 52.175926 Tz (molecules, ) Tj 3.363889 0 Td 53.472222 Tz (such ) Tj 1.497222 0 Td 51.851852 Tz (as ) Tj 0.855556 0 Td 77.777778 Tz (NSC ) Tj 1.613889 0 Td 61.574074 Tz (48300 ) Tj 2.061111 0 Td 44.290123 Tz (\(as ) Tj 1.011111 0 Td 54.282407 Tz (provided ) Tj 2.8 0 Td 45.910494 Tz (structurally ) Tj 3.519444 0 Td 63.194444 Tz (on ) Tj 52.857143 0 0 52.857143 0 1624.839416 Tm 24.613514 0 Td 55.968468 Tz (page ) Tj 1.57027 0 Td 39.414414 Tz (6, ) Tj 0.662162 0 Td 53.603604 Tz (above\) ) Tj 2.137838 0 Td 52.815315 Tz (demonstrated ) Tj 3.991892 0 Td 53.153153 Tz (potency ) Tj 2.440541 0 Td 40.990991 Tz (in ) Tj 0.756757 0 Td 56.056056 Tz (nanomolar ) Tj 3.178378 0 Td 62.537538 Tz (concen ) Tj 50.285714 0 0 50.285714 0 1583.739953 Tm 12.548295 0 Td 59.659091 Tz (CF ) Tj 13.303977 0 Td 46.815814 Tz (trations ) Tj 2.485795 0 Td 49.715909 Tz (as ) Tj 0.855114 0 Td 52.728994 Tz (competitive ) Tj 3.678977 0 Td 79.545455 Tz (ATX ) Tj 1.670455 0 Td 45.49759 Tz (inhibitors. ) Tj 3.241477 0 Td 56.344697 Tz (Within ) Tj 2.267045 0 Td 50.820707 Tz (the ) Tj 1.133523 0 Td 46.953914 Tz (series ) Tj 1.928977 0 Td 59.659091 Tz (of ) Tj 51.428571 0 0 51.428571 0 1542.573281 Tm 25.297222 0 Td 52.777778 Tz (analogs ) Tj 2.469444 0 Td 54.282407 Tz (provided ) Tj 2.858333 0 Td 57.037037 Tz (above ) Tj 2.022222 0 Td 48.611111 Tz (\(B, ) Tj 1.147222 0 Td 56.712963 Tz (C, ) Tj 0.933333 0 Td 59.41358 Tz (and ) Tj 1.380556 0 Td 53.472222 Tz (D, ) Tj 0.933333 0 Td 55.740741 Tz (based ) Tj 1.925 0 Td 59.953704 Tz (on ) Tj 0.991667 0 Td 58.333333 Tz (backbone ) Tj 51.428571 0 0 51.428571 0 1502.390476 Tm 24.266667 0 Td 45.37037 Tz (35 ) Tj 1.030556 0 Td 64.00463 Tz (compound ) Tj 3.247222 0 Td 51.851852 Tz (A\), ) Tj 1.147222 0 Td 53.472222 Tz (unexpectedly ) Tj 4.083333 0 Td 32.407407 Tz (it ) Tj 0.602778 0 Td 60.493827 Tz (was ) Tj 1.302778 0 Td 57.037037 Tz (found ) Tj 1.886111 0 Td 46.990741 Tz (that ) Tj 1.322222 0 Td 46.759259 Tz (certain ) Tj 2.216667 0 Td 91.820988 Tz (mem ) Tj 51.428571 0 0 51.428571 0 1458.78744 Tm 25.277778 0 Td 51.041667 Tz (bers ) Tj 1.438889 0 Td 59.953704 Tz (of ) Tj 0.836111 0 Td 49.907407 Tz (these ) Tj 1.711111 0 Td 45.37037 Tz (series ) Tj 1.827778 0 Td 50.411523 Tz (exhibited ) Tj 2.936111 0 Td 46.450617 Tz (effective ) Tj 2.702778 0 Td 49.96142 Tz (competitive, ) Tj 3.830556 0 Td 73.240741 Tz (uncom ) Tj 47.428571 0 0 47.428571 0 1416.004635 Tm 16.024096 0 Td 73.795181 Tz (C ) Tj 8.813253 0 Td 73.795181 Tz (C ) Tj 2.593373 0 Td 48.75753 Tz (petitive ) Tj 2.53012 0 Td 65.595716 Tz (and ) Tj 1.433735 0 Td 63.955823 Tz (mixed ) Tj 2.150602 0 Td 72.916667 Tz (mode ) Tj 1.918675 0 Td 85.508701 Tz (ATX ) Tj 1.771084 0 Td 50.60241 Tz (inhibition ) Tj 3.310241 0 Td 61.016794 Tz (mechanisms. ) Tj 4.322289 0 Td 63.253012 Tz (Both ) Tj 51.428571 0 0 51.428571 0 1375.694915 Tm 25.297222 0 Td 51.557239 Tz (competitive ) Tj 3.558333 0 Td 60.493827 Tz (and ) Tj 1.263889 0 Td 60.277778 Tz (mixed ) Tj 2.002778 0 Td 66.435185 Tz (mode ) Tj 1.788889 0 Td 45.694444 Tz (inhibitors ) Tj 2.955556 0 Td 58.333333 Tz (were ) Tj 1.555556 0 Td 51.851852 Tz (able ) Tj 1.4 0 Td 46.990741 Tz (to ) Tj 0.738889 0 Td 52.777778 Tz (achieve ) Tj 51.428571 0 0 51.428571 0 1332.916767 Tm 25.375 0 Td 66.435185 Tz (100% ) Tj 1.75 0 Td 46.990741 Tz (inhibition ) Tj 2.916667 0 Td 45.37037 Tz (at ) Tj 0.641667 0 Td 46.254209 Tz (saturation, ) Tj 3.169444 0 Td 58.333333 Tz (due ) Tj 1.186111 0 Td 43.75 Tz (to ) Tj 0.680556 0 Td 44.722222 Tz (their ) Tj 1.419444 0 Td 43.981481 Tz (ability ) Tj 1.963889 0 Td 46.990741 Tz (to ) Tj 0.680556 0 Td 54.282407 Tz (bind ) Tj 1.380556 0 Td 50.231481 Tz (to ) Tj 0.719444 0 Td 48.611111 Tz (the ) Tj 51.428571 0 0 51.428571 0 1295.91497 Tm 24.247222 0 Td 48.611111 Tz (40 ) Tj 1.030556 0 Td 63.734568 Tz (enzyme ) Tj 2.508333 0 Td 48.611111 Tz (to ) Tj 0.836111 0 Td 58.333333 Tz (form ) Tj 1.652778 0 Td 55.092593 Tz (an ) Tj 0.952778 0 Td 52.459491 Tz (enzyme-inhibitor ) Tj 5.269444 0 Td 55.092593 Tz (complex. ) Tj 2.936111 0 Td 48.611111 Tz (In ) Tj 0.855556 0 Td 45.37037 Tz (contrast, ) Tj 51.428571 0 0 51.428571 0 1252.554468 Tm 25.277778 0 Td 50.771605 Tz (the ) Tj 1.244444 0 Td 53.347578 Tz (uncompetitive ) Tj 4.452778 0 Td 45.075758 Tz (inhibitors, ) Tj 3.305556 0 Td 45.37037 Tz (at ) Tj 0.855556 0 Td 48.287037 Tz (Saturating ) Tj 3.208333 0 Td 48.82716 Tz (concentrations, ) Tj 51.428571 0 0 51.428571 0 1212.476886 Tm 25.297222 0 Td 53.796296 Tz (could ) Tj 1.827778 0 Td 50.771605 Tz (not ) Tj 1.088889 0 Td 53.472222 Tz (completely ) Tj 3.402778 0 Td 45.833333 Tz (inhibit ) Tj 2.061111 0 Td 48.905724 Tz (hydrolysis, ) Tj 3.422222 0 Td 48.611111 Tz (as ) Tj 0.777778 0 Td 51.041667 Tz (they ) Tj 1.419444 0 Td 55.632716 Tz (binded ) Tj 2.177778 0 Td 53.472222 Tz (only ) Tj 51.428571 0 0 51.428571 0 1170.840336 Tm 25.277778 0 Td 45.37037 Tz (to ) Tj 0.816667 0 Td 48.611111 Tz (the ) Tj 1.069444 0 Td 53.472222 Tz (enzyme-substrate ) Tj 5.327778 0 Td 55.497685 Tz (complex. ) Tj 2.877778 0 Td 58.981481 Tz (These ) Tj 2.002778 0 Td 48.611111 Tz (differences ) Tj 3.383333 0 Td 47.685185 Tz (clearly ) Tj 51.428571 0 0 51.428571 0 1127.140097 Tm 25.316667 0 Td 51.851852 Tz (Suggest ) Tj 2.313889 0 Td 46.990741 Tz (that ) Tj 1.283333 0 Td 53.098291 Tz (uncompetitive ) Tj 4.316667 0 Td 46.018519 Tz (inhibitors ) Tj 2.975 0 Td 38.888889 Tz (fail ) Tj 1.088889 0 Td 48.611111 Tz (to ) Tj 0.758333 0 Td 45.775463 Tz (interact ) Tj 2.352778 0 Td 53.472222 Tz (with ) Tj 1.477778 0 Td 49.691358 Tz (the ) Tj 61.428571 0 0 61.428571 0 1088.226506 Tm 20.3 0 Td 39.341085 Tz (45 ) Tj 0.87907 0 Td 52.228682 Tz (same ) Tj 1.465116 0 Td 44.186047 Tz (binding ) Tj 2.051163 0 Td 42.635659 Tz (pocket, ) Tj 2.002326 0 Td 43.79845 Tz (thereby ) Tj 2.034884 0 Td 43.712317 Tz (providing ) Tj 2.555814 0 Td 48.837209 Tz (a ) Tj 0.488372 0 Td 41.24031 Tz (basis ) Tj 1.465116 0 Td 40.697674 Tz (for ) Tj 0.911628 0 Td 39.922481 Tz (further ) Tj 51.428571 0 0 51.428571 0 1044.924171 Tm 25.297222 0 Td 47.364672 Tz (investigation ) Tj 3.888889 0 Td 52.662037 Tz (with ) Tj 1.458333 0 Td 49.691358 Tz (the ) Tj 1.05 0 Td 51.851852 Tz (phenylthiourea ) Tj 4.511111 0 Td 47.890947 Tz (reactants ) Tj 2.761111 0 Td 48.611111 Tz (as ) Tj 0.758333 0 Td 56.17284 Tz (intermedi ) Tj 51.428571 0 0 51.428571 0 1003.113956 Tm 25.297222 0 Td 46.990741 Tz (ates ) Tj 1.438889 0 Td 48.611111 Tz (for ) Tj 1.166667 0 Td 47.222222 Tz (further ) Tj 2.294444 0 Td 48.251029 Tz (reactions ) Tj 2.916667 0 Td 51.041667 Tz (and, ) Tj 1.555556 0 Td 50.636574 Tz (possibly ) Tj 2.8 0 Td 60.763889 Tz (more ) Tj 1.788889 0 Td 48.341049 Tz (importantly, ) Tj 32.857143 0 0 32.857143 0 970 Tm 25.778261 0 Td 101.449275 Tz (OMe ) Tj 2.891304 0 Td 68.478261 Tz (Cl ) Tj 51.428571 0 0 51.428571 0 961.831847 Tm 25.297222 0 Td 50.555556 Tz (permitting ) Tj 3.286111 0 Td 58.333333 Tz (a ) Tj 0.661111 0 Td 60.763889 Tz (more ) Tj 1.730556 0 Td 50.231481 Tz (in-depth ) Tj 2.683333 0 Td 44.444444 Tz (ability ) Tj 2.158333 0 Td 46.990741 Tz (to ) Tj 0.875 0 Td 54.012346 Tz (determine ) Tj 3.15 0 Td 50.771605 Tz (the ) Tj 1.166667 0 Td 48.611111 Tz (actual ) Tj 51.428571 0 0 51.428571 0 919.886392 Tm 25.316667 0 Td 46.8107 Tz (structure ) Tj 2.780556 0 Td 59.953704 Tz (of ) Tj 0.816667 0 Td 78.858025 Tz (ATX ) Tj 1.691667 0 Td 42.669753 Tz (itself ) Tj 1.711111 0 Td 46.450617 Tz (for ) Tj 1.108333 0 Td 47.530864 Tz (future ) Tj 1.963889 0 Td 53.652263 Tz (computer, ) Tj 3.15 0 Td 40.185185 Tz (etc., ) Tj 1.516667 0 Td 56.712963 Tz (modeling ) Tj 51.428571 0 0 51.428571 0 879.478555 Tm 24.266667 0 Td 45.37037 Tz (50 ) Tj 1.030556 0 Td 51.851852 Tz (approaches. ) Tj 3.616667 0 Td 51.851852 Tz (Future ) Tj 1.963889 0 Td 53.347578 Tz (computational ) Tj 4.297222 0 Td 46.666667 Tz (tools ) Tj 1.536111 0 Td 46.990741 Tz (will ) Tj 1.244444 0 Td 48.971193 Tz (therefore ) Tj 2.761111 0 Td 49.074074 Tz (require ) Tj 51.428571 0 0 51.428571 0 834.81733 Tm 25.297222 0 Td 52.391975 Tz (experimental ) Tj 3.947222 0 Td 45.601852 Tz (identification ) Tj 4.025 0 Td 56.712963 Tz (of ) Tj 0.777778 0 Td 46.666667 Tz (inhibition ) Tj 3.033333 0 Td 56.565657 Tz (mechanisms, ) Tj 3.927778 0 Td 59.62963 Tz (which ) Tj 49.61039 0 0 49.61039 0 794.357895 Tm 13.989005 0 Td 67.190227 Tz (OMe ) Tj 12.215183 0 Td 49.552792 Tz (will ) Tj 1.410995 0 Td 55.095986 Tz (allow ) Tj 1.935079 0 Td 49.272833 Tz (for ) Tj 1.128796 0 Td 50.39267 Tz (the ) Tj 1.148953 0 Td 58.638743 Tz (development ) Tj 4.091885 0 Td 58.791449 Tz (of ) Tj 0.866754 0 Td 46.61322 Tz (distinct ) Tj 2.479319 0 Td 58.791449 Tz (models ) Tj 2.418848 0 Td 49.272833 Tz (for ) Tj 1.068325 0 Td 87.347295 Tz (com ) Tj 51.428571 0 0 51.428571 0 751.407895 Tm 25.297222 0 Td 57.79321 Tz (pounds ) Tj 2.275 0 Td 53.472222 Tz (with ) Tj 1.477778 0 Td 55.092593 Tz (a ) Tj 0.525 0 Td 51.851852 Tz (shared ) Tj 2.080556 0 Td 46.666667 Tz (inhibition ) Tj 3.013889 0 Td 57.685185 Tz (mechanism. ) Tj 51.428571 0 0 51.428571 0 710.435644 Tm 26.016667 0 Td 69.675926 Tz (Of ) Tj 0.913889 0 Td 48.611111 Tz (additional ) Tj 3.072222 0 Td 46.990741 Tz (particular ) Tj 2.936111 0 Td 44.560185 Tz (interest ) Tj 2.294444 0 Td 45.37037 Tz (in ) Tj 0.7 0 Td 49.691358 Tz (the ) Tj 0.991667 0 Td 78.858025 Tz (ATX ) Tj 1.575 0 Td 46.990741 Tz (inhibition ) Tj 2.975 0 Td 44.074074 Tz (field ) Tj 51.428571 0 0 51.428571 0 671.665832 Tm 24.266667 0 Td 45.37037 Tz (55 ) Tj 1.030556 0 Td 38.888889 Tz (is ) Tj 0.797222 0 Td 49.691358 Tz (the ) Tj 1.166667 0 Td 47.170782 Tz (potential ) Tj 2.877778 0 Td 47.530864 Tz (for ) Tj 1.166667 0 Td 52.824074 Tz (developing ) Tj 3.480556 0 Td 51.851852 Tz (a ) Tj 0.622222 0 Td 61.934156 Tz (compounds ) Tj 3.655556 0 Td 46.180556 Tz (that ) Tj 1.4 0 Td 47.800926 Tz (exhibits ) Tj 51.428571 0 0 51.428571 0 629.805917 Tm 25.316667 0 Td 44.781145 Tz (specificity ) Tj 3.091667 0 Td 48.611111 Tz (for ) Tj 0.952778 0 Td 76.697531 Tz (ATX ) Tj 1.477778 0 Td 48.611111 Tz (alone. ) Tj 1.905556 0 Td 46.990741 Tz (In ) Tj 0.7 0 Td 43.75 Tz (actuality, ) Tj 2.761111 0 Td 34.027778 Tz (it ) Tj 0.486111 0 Td 53.240741 Tz (appears ) Tj 2.352778 0 Td 46.180556 Tz (that ) Tj 1.225 0 Td 46.8107 Tz (inhibitor ) Tj 51.428571 0 0 51.428571 0 587.995068 Tm 25.316667 0 Td 44.781145 Tz (specificity ) Tj 3.15 0 Td 46.990741 Tz (in ) Tj 0.758333 0 Td 49.691358 Tz (the ) Tj 1.069444 0 Td 75.617284 Tz (NPP ) Tj 1.536111 0 Td 51.851852 Tz (family ) Tj 2.061111 0 Td 52.932099 Tz (has ) Tj 1.147222 0 Td 50.87963 Tz (previously ) Tj 3.286111 0 Td 49.691358 Tz (not ) Tj 1.05 0 Td 58.333333 Tz (been ) Tj 1.555556 0 Td 76.157407 Tz (exam ) Tj 51.428571 0 0 51.428571 0 544.340426 Tm 25.297222 0 Td 47.314815 Tz (ined. ) Tj 1.730556 0 Td 58.333333 Tz (Three ) Tj 2.1 0 Td 62.962963 Tz (members ) Tj 3.013889 0 Td 56.712963 Tz (of ) Tj 0.991667 0 Td 47.530864 Tz (the ) Tj 1.225 0 Td 74.537037 Tz (NPP ) Tj 1.691667 0 Td 62.654321 Tz (enzyme ) Tj 2.625 0 Td 48.148148 Tz (family, ) Tj 2.411111 0 Td 68.865741 Tz (NPP2 ) Tj 51.428571 0 0 51.428571 0 504.162562 Tm 25.316667 0 Td 56.712963 Tz (\(ATX\), ) Tj 2.255556 0 Td 68.865741 Tz (NPP6 ) Tj 1.847222 0 Td 58.333333 Tz (and ) Tj 1.225 0 Td 61.574074 Tz (NPP7, ) Tj 2.061111 0 Td 51.203704 Tz (share ) Tj 1.691667 0 Td 49.691358 Tz (the ) Tj 1.05 0 Td 44.907407 Tz (ability ) Tj 2.061111 0 Td 43.75 Tz (to ) Tj 0.7 0 Td 54.012346 Tz (hydrolyze ) Tj 3.111111 0 Td 59.953704 Tz (lyso ) Tj 51.428571 0 0 51.428571 0 463.027397 Tm 24.286111 0 Td 45.37037 Tz (60 ) Tj 0.991667 0 Td 50.925926 Tz (phospholipids, ) Tj 4.394444 0 Td 60.493827 Tz (and ) Tj 1.225 0 Td 48.611111 Tz (therefore ) Tj 2.780556 0 Td 56.388889 Tz (might ) Tj 1.788889 0 Td 59.953704 Tz (be ) Tj 0.836111 0 Td 54.282407 Tz (expected ) Tj 2.722222 0 Td 46.990741 Tz (to ) Tj 0.7 0 Td 56.712963 Tz (have ) Tj 1.497222 0 Td 64.814815 Tz (some ) Tj 51.428571 0 0 51.428571 0 420.738386 Tm 25.297222 0 Td 50.925926 Tz (overlap ) Tj 2.352778 0 Td 45.37037 Tz (in ) Tj 0.719444 0 Td 46.018519 Tz (their ) Tj 1.536111 0 Td 50.084175 Tz (recognition ) Tj 3.5 0 Td 56.712963 Tz (of ) Tj 0.777778 0 Td 44.781145 Tz (inhibitors. ) Tj 3.130556 0 Td 66.435185 Tz (As ) Tj 0.972222 0 Td 50.411523 Tz (autotaxin ) Tj 2.916667 0 Td 38.888889 Tz (is ) Tj 0.661111 0 Td 50.771605 Tz (the ) Tj 49.61039 0 0 49.61039 0 378.406863 Tm 23.966754 0 Td 33.595113 Tz (I ) Tj 2.257592 0 Td 56.151832 Tz (primary ) Tj 2.580105 0 Td 54.872019 Tz (source ) Tj 2.19712 0 Td 49.272833 Tz (for ) Tj 1.068325 0 Td 76.148924 Tz (LPC ) Tj 1.552094 0 Td 54.424084 Tz (conversion ) Tj 3.487173 0 Td 47.033159 Tz (to ) Tj 0.786126 0 Td 50.39267 Tz (the ) Tj 1.088482 0 Td 50.812609 Tz (targeted ) Tj 2.660733 0 Td 72.789412 Tz (LPA ) Tj 1.51178 0 Td 64.950553 Tz (cul ) Tj 51.428571 0 0 51.428571 0 336.579618 Tm 25.297222 0 Td 38.888889 Tz (prit, ) Tj 1.458333 0 Td 48.611111 Tz (the ) Tj 1.127778 0 Td 43.981481 Tz (ability ) Tj 2.119444 0 Td 45.37037 Tz (to ) Tj 0.797222 0 Td 51.262626 Tz (concentrate ) Tj 3.636111 0 Td 49.691358 Tz (the ) Tj 1.147222 0 Td 47.863248 Tz (effectiveness ) Tj 4.005556 0 Td 58.333333 Tz (of ) Tj 0.836111 0 Td 58.333333 Tz (an ) Tj 0.913889 0 Td 78.858025 Tz (ATX ) Tj 51.428571 0 0 51.428571 0 294.763057 Tm 25.297222 0 Td 46.8107 Tz (inhibitor ) Tj 2.819444 0 Td 61.574074 Tz (on ) Tj 1.069444 0 Td 45.37037 Tz (that ) Tj 1.419444 0 Td 47.530864 Tz (structure ) Tj 2.858333 0 Td 53.796296 Tz (alone ) Tj 1.925 0 Td 51.851852 Tz (\(without ) Tj 2.819444 0 Td 48.611111 Tz (the ) Tj 1.205556 0 Td 50.968013 Tz (appreciable ) Tj 49.761905 0 0 49.761905 0 253.423077 Tm 19.211483 0 Td 53.588517 Tz (F ) Tj 5.888038 0 Td 45.215311 Tz (65 ) Tj 1.02488 0 Td 48.750665 Tz (potential ) Tj 2.913876 0 Td 50.239234 Tz (for ) Tj 1.125359 0 Td 58.054226 Tz (wasted ) Tj 2.3311 0 Td 60.76555 Tz (amounts ) Tj 2.813397 0 Td 60.287081 Tz (of ) Tj 0.884211 0 Td 48.750665 Tz (inhibitor ) Tj 2.853589 0 Td 54.92823 Tz (being ) Tj 1.929187 0 Td 56.100478 Tz (used ) Tj 1.627751 0 Td 61.961722 Tz (up ) Tj 1.02488 0 Td 48.564593 Tz (in ) Tj 49.428571 0 0 49.428571 0 215.917869 Tm 13.433526 0 Td 67.43738 Tz (OMe ) Tj 12.887283 0 Td 49.229287 Tz (inhibiting ) Tj 3.075145 0 Td 53.27553 Tz (other ) Tj 1.719653 0 Td 61.115125 Tz (NPP-type ) Tj 3.054913 0 Td 60.693642 Tz (enzymes\) ) Tj 3.075145 0 Td 40.462428 Tz (is ) Tj 0.647399 0 Td 53.949904 Tz (a ) Tj 0.485549 0 Td 46.082209 Tz (significant, ) Tj 3.459538 0 Td 44.315992 Tz (albeit, ) Tj 2.023121 0 Td 52.263969 Tz (as ) Tj 51.428571 0 0 51.428571 0 170.960854 Tm 25.297222 0 Td 49.691358 Tz (noted, ) Tj 1.983333 0 Td 58.981481 Tz (unexamined ) Tj 3.694444 0 Td 44.020062 Tz (possibility. ) Tj 3.363889 0 Td 62.654321 Tz (The ) Tj 1.302778 0 Td 48.611111 Tz (inventive ) Tj 2.819444 0 Td 53.652263 Tz (pipemidic ) Tj 3.072222 0 Td 51.851852 Tz (acid ) Tj ET Q endstream endobj 292 0 obj << /Length 1 >> stream q endstream endobj 293 0 obj << /Length 37482 >> stream Q q 0.24 0 0 0.24 0 0 cm BT /F1 1 Tf 3 Tr 62.857143 0 0 62.857143 0 3023 Tm 17.325 0 Td 83.522727 Tz (US ) Tj 1.240909 0 Td 57.154882 Tz (8,497,371 ) Tj 3.388636 0 Td 74.242424 Tz (B2 ) Tj 52.857143 0 0 52.857143 0 2968 Tm 14.245946 0 Td 72.522523 Tz (13 ) Tj 51.428571 0 0 51.428571 0 2917.790476 Tm 6.358333 0 Td 47.638889 Tz (derivative ) Tj 3.033333 0 Td 61.934156 Tz (compounds ) Tj 3.577778 0 Td 53.20216 Tz (unexpectedly ) Tj 4.025 0 Td 48.148148 Tz (exhibit ) Tj 2.197222 0 Td 55.092593 Tz (such ) Tj 1.516667 0 Td 58.333333 Tz (a ) Tj 0.505556 0 Td 72.376543 Tz (phenom ) Tj 51.428571 0 0 51.428571 0 2872.572509 Tm 6.358333 0 Td 58.333333 Tz (enon ) Tj 1.652778 0 Td 59.953704 Tz (of ) Tj 0.855556 0 Td 45.075758 Tz (selectivity ) Tj 3.247222 0 Td 47.530864 Tz (for ) Tj 1.030556 0 Td 78.858025 Tz (ATX ) Tj 1.652778 0 Td 66.111111 Tz (among ) Tj 2.255556 0 Td 48.611111 Tz (the ) Tj 1.108333 0 Td 75.617284 Tz (NPP ) Tj 1.575 0 Td 52.662037 Tz (isoforms ) Tj 2.819444 0 Td 54.282407 Tz (with ) Tj 51.428571 0 0 51.428571 0 2829.762219 Tm 6.358333 0 Td 54.552469 Tz (demonstrated ) Tj 4.083333 0 Td 51.527778 Tz (preference ) Tj 3.286111 0 Td 47.530864 Tz (for ) Tj 0.991667 0 Td 53.20216 Tz (phospholipid ) Tj 4.025 0 Td 45.664983 Tz (substrates. ) Tj 51.428571 0 0 51.428571 0 2787.945409 Tm 7.116667 0 Td 35.648148 Tz (It ) Tj 0.544444 0 Td 40.509259 Tz (is ) Tj 0.622222 0 Td 49.259259 Tz (preferable ) Tj 3.072222 0 Td 46.180556 Tz (that ) Tj 1.225 0 Td 55.092593 Tz (such ) Tj 1.438889 0 Td 54.012346 Tz (compositions ) Tj 4.025 0 Td 56.712963 Tz (be ) Tj 0.816667 0 Td 46.990741 Tz (orally ) Tj 1.827778 0 Td 47.138047 Tz (ingestable, ) Tj 51.428571 0 0 51.428571 0 2741.735484 Tm 6.338889 0 Td 52.932099 Tz (but ) Tj 1.186111 0 Td 51.851852 Tz (they ) Tj 1.555556 0 Td 55.902778 Tz (may, ) Tj 1.594444 0 Td 50.231481 Tz (as ) Tj 0.913889 0 Td 52.5 Tz (noted ) Tj 1.808333 0 Td 52.391975 Tz (above, ) Tj 2.177778 0 Td 58.333333 Tz (be ) Tj 0.933333 0 Td 53.472222 Tz (provided ) Tj 2.858333 0 Td 47.530864 Tz (for ) Tj 1.108333 0 Td 50.673401 Tz (intravenous ) Tj 40 0 0 40 0 2703 Tm 8.175 0 Td 63.194444 Tz (introduction ) Tj 4.775 0 Td 66.666667 Tz (as ) Tj 1.05 0 Td 60 Tz (well. ) Tj 51.428571 0 0 51.428571 0 2654.522222 Tm 7.116667 0 Td 46.990741 Tz (In ) Tj 0.875 0 Td 53.148148 Tz (terms ) Tj 1.925 0 Td 58.333333 Tz (of ) Tj 0.894444 0 Td 50.771605 Tz (the ) Tj 1.205556 0 Td 57.523148 Tz (form ) Tj 1.730556 0 Td 54.282407 Tz (Such ) Tj 1.613889 0 Td 53.742284 Tz (compositions ) Tj 4.2 0 Td 68.055556 Tz (may ) Tj 1.536111 0 Td 46.018519 Tz (take, ) Tj 1.672222 0 Td 59.41358 Tz (any ) Tj 51.428571 0 0 51.428571 0 2611.583535 Tm 6.358333 0 Td 46.990741 Tz (orally ) Tj 1.866667 0 Td 49.259259 Tz (ingestable ) Tj 3.111111 0 Td 58.333333 Tz (form ) Tj 1.594444 0 Td 38.888889 Tz (is ) Tj 0.641667 0 Td 47.170782 Tz (possible. ) Tj 2.722222 0 Td 54.282407 Tz (This ) Tj 1.497222 0 Td 36.458333 Tz (list ) Tj 1.030556 0 Td 48.251029 Tz (includes, ) Tj 2.8 0 Td 52.777778 Tz (without ) Tj 51.428571 0 0 51.428571 0 2567.334168 Tm 6.358333 0 Td 45.37037 Tz (limitation, ) Tj 3.325 0 Td 44.965278 Tz (liquids, ) Tj 2.508333 0 Td 46.450617 Tz (liquid ) Tj 1.983333 0 Td 48.971193 Tz (capsules, ) Tj 2.936111 0 Td 43.75 Tz (tablets, ) Tj 2.430556 0 Td 52.391975 Tz (coated ) Tj 2.177778 0 Td 43.344907 Tz (tablets, ) Tj 51.428571 0 0 51.428571 0 2521.220339 Tm 6.358333 0 Td 46.990741 Tz (minitablets, ) Tj 3.558333 0 Td 51.041667 Tz (capsules ) Tj 2.625 0 Td 52.662037 Tz (with ) Tj 1.438889 0 Td 47.962963 Tz (individual ) Tj 3.052778 0 Td 50.771605 Tz (beads, ) Tj 1.983333 0 Td 58.333333 Tz (and ) Tj 1.186111 0 Td 49.691358 Tz (the ) Tj 1.05 0 Td 40.185185 Tz (like. ) Tj 1.419444 0 Td 42.12963 Tz (If ) Tj 0.583333 0 Td 50.231481 Tz (in ) Tj 51.428571 0 0 51.428571 0 2479.606742 Tm 6.358333 0 Td 52.932099 Tz (coated ) Tj 2.138889 0 Td 45.37037 Tz (tablet ) Tj 1.866667 0 Td 52.5 Tz (form, ) Tj 1.827778 0 Td 54.282407 Tz (such ) Tj 1.575 0 Td 53.472222 Tz (compositions ) Tj 4.122222 0 Td 68.055556 Tz (may ) Tj 1.458333 0 Td 58.333333 Tz (be ) Tj 0.952778 0 Td 55.092593 Tz (of ) Tj 0.836111 0 Td 50.411523 Tz (Sustained ) Tj 51.428571 0 0 51.428571 0 2435.764497 Tm 6.358333 0 Td 48.148148 Tz (release ) Tj 2.138889 0 Td 47.314815 Tz (type, ) Tj 1.536111 0 Td 59.41358 Tz (and ) Tj 1.186111 0 Td 68.055556 Tz (may ) Tj 1.361111 0 Td 50.925926 Tz (include ) Tj 2.255556 0 Td 55.092593 Tz (a ) Tj 0.447222 0 Td 53.796296 Tz (water ) Tj 1.711111 0 Td 49.331276 Tz (insoluble ) Tj 2.780556 0 Td 50.771605 Tz (but ) Tj 1.030556 0 Td 56.17284 Tz (permeable ) Tj 51.428571 0 0 51.428571 0 2393.831788 Tm 6.358333 0 Td 47.800926 Tz (film ) Tj 1.536111 0 Td 50.925926 Tz (coating ) Tj 2.508333 0 Td 53.030303 Tz (Surrounding ) Tj 3.85 0 Td 55.092593 Tz (a ) Tj 0.661111 0 Td 52.662037 Tz (core ) Tj 1.594444 0 Td 45.910494 Tz (tablet ) Tj 1.983333 0 Td 59.41358 Tz (and ) Tj 1.380556 0 Td 58.333333 Tz (a ) Tj 0.7 0 Td 44.830247 Tz (particulate, ) Tj 51.428571 0 0 51.428571 0 2349.352941 Tm 6.338889 0 Td 49.305556 Tz (water-soluble, ) Tj 4.433333 0 Td 54.282407 Tz (pore-forming ) Tj 4.258333 0 Td 48.611111 Tz (material ) Tj 2.683333 0 Td 50.771605 Tz (dispersed ) Tj 3.052778 0 Td 51.311728 Tz (within ) Tj 2.177778 0 Td 49.691358 Tz (the ) Tj 51.428571 0 0 51.428571 0 2306.523409 Tm 6.358333 0 Td 47.800926 Tz (film ) Tj 1.302778 0 Td 47.800926 Tz (coating. ) Tj 2.45 0 Td 59.143519 Tz (Such ) Tj 1.555556 0 Td 51.851852 Tz (a ) Tj 0.447222 0 Td 55.092593 Tz (system ) Tj 2.138889 0 Td 50.231481 Tz (thus ) Tj 1.341667 0 Td 51.851852 Tz (provides ) Tj 2.605556 0 Td 56.712963 Tz (an ) Tj 0.836111 0 Td 54.166667 Tz (osmotic ) Tj 2.411111 0 Td 49.826389 Tz (gradient ) Tj 51.428571 0 0 51.428571 0 2262.462455 Tm 6.358333 0 Td 58.333333 Tz (and ) Tj 1.225 0 Td 53.703704 Tz (channel ) Tj 2.430556 0 Td 56.018519 Tz (forming ) Tj 2.508333 0 Td 51.851852 Tz (system. ) Tj 2.352778 0 Td 51.388889 Tz (Typical ) Tj 2.352778 0 Td 50.231481 Tz (coatings ) Tj 2.566667 0 Td 56.712963 Tz (have ) Tj 1.516667 0 Td 53.06713 Tz (included ) Tj 51.428571 0 0 51.428571 0 2220.271028 Tm 6.358333 0 Td 55.092593 Tz (carnauba ) Tj 2.780556 0 Td 57.523148 Tz (wax, ) Tj 1.555556 0 Td 49.826389 Tz (cysteine ) Tj 2.527778 0 Td 50.694444 Tz (hydrochloride, ) Tj 4.413889 0 Td 55.34188 Tz (hydroxypropyl ) Tj 4.530556 0 Td 68.865741 Tz (meth ) Tj 51.428571 0 0 51.428571 0 2176.519527 Tm 6.338889 0 Td 46.450617 Tz (ylcellulose, ) Tj 3.597222 0 Td 61.213992 Tz (magnesium ) Tj 3.577778 0 Td 43.930041 Tz (Stearate, ) Tj 2.644444 0 Td 48.813657 Tz (microcrystalline ) Tj 4.919444 0 Td 45.37037 Tz (cellulose, ) Tj 51.428571 0 0 51.428571 0 2131.320191 Tm 6.358333 0 Td 52.391975 Tz (polyethylene ) Tj 3.927778 0 Td 50.231481 Tz (glycol ) Tj 2.022222 0 Td 59.41358 Tz (and ) Tj 1.263889 0 Td 49.826389 Tz (titanium ) Tj 2.625 0 Td 48.611111 Tz (dioxide. ) Tj 2.547222 0 Td 56.388889 Tz (Other ) Tj 1.866667 0 Td 48.611111 Tz (therapeutic ) Tj 51.428571 0 0 51.428571 0 2085.626943 Tm 6.358333 0 Td 51.311728 Tz (agents ) Tj 2.236111 0 Td 66.975309 Tz (may ) Tj 1.575 0 Td 58.333333 Tz (be ) Tj 1.05 0 Td 51.851852 Tz (included ) Tj 2.858333 0 Td 52.662037 Tz (with ) Tj 1.594444 0 Td 50.555556 Tz (these ) Tj 1.847222 0 Td 50.555556 Tz (anticancer ) Tj 3.383333 0 Td 49.259259 Tz (\(autotaxin ) Tj 51.428571 0 0 51.428571 0 2043.210063 Tm 6.358333 0 Td 46.548822 Tz (inhibiting\) ) Tj 3.286111 0 Td 50.771605 Tz (agents ) Tj 2.080556 0 Td 48.611111 Tz (as ) Tj 0.816667 0 Td 47.314815 Tz (well, ) Tj 1.633333 0 Td 50.231481 Tz (as ) Tj 0.836111 0 Td 54.282407 Tz (long ) Tj 1.477778 0 Td 51.851852 Tz (as ) Tj 0.875 0 Td 48.148148 Tz (neither ) Tj 2.236111 0 Td 45.046296 Tz (interferes ) Tj 2.936111 0 Td 54.282407 Tz (with ) Tj 51.428571 0 0 51.428571 0 1997.003096 Tm 6.338889 0 Td 50.771605 Tz (the ) Tj 1.069444 0 Td 48.112536 Tz (effectiveness ) Tj 3.947222 0 Td 58.333333 Tz (of ) Tj 0.777778 0 Td 50.771605 Tz (the ) Tj 1.088889 0 Td 51.203704 Tz (other ) Tj 1.691667 0 Td 43.75 Tz (in ) Tj 0.738889 0 Td 49.691358 Tz (the ) Tj 1.069444 0 Td 48.611111 Tz (user's ) Tj 1.905556 0 Td 52.5 Tz (body. ) Tj 38.571429 0 0 38.571429 0 1923 Tm 9.851852 0 Td 97.762346 Tz (DETAILED ) Tj 4.977778 0 Td 94.276094 Tz (DESCRIPTION ) Tj 6.533333 0 Td 99.382716 Tz (OF ) Tj 1.4 0 Td 106.584362 Tz (THE ) Tj 2.177778 0 Td 101.303155 Tz (PREFERRED ) Tj 38.571429 0 0 38.571429 0 1880 Tm 16.592593 0 Td 107.239057 Tz (EMBODIMENTS ) Tj 51.428571 0 0 51.428571 0 1788.538259 Tm 7.097222 0 Td 62.654321 Tz (The ) Tj 1.361111 0 Td 45.775463 Tz (specific ) Tj 2.469444 0 Td 61.934156 Tz (compounds ) Tj 3.577778 0 Td 53.472222 Tz (below, ) Tj 2.177778 0 Td 48.611111 Tz (as ) Tj 0.836111 0 Td 51.851852 Tz (well ) Tj 1.497222 0 Td 50.231481 Tz (as ) Tj 0.855556 0 Td 49.691358 Tz (the ) Tj 1.147222 0 Td 52.211934 Tz (following ) Tj 51.428571 0 0 51.428571 0 1746.46181 Tm 6.358333 0 Td 51.851852 Tz (exemplified ) Tj 3.558333 0 Td 57.87037 Tz (methods ) Tj 2.586111 0 Td 53.472222 Tz (of ) Tj 0.719444 0 Td 54.73251 Tz (producing ) Tj 3.072222 0 Td 52.5 Tz (using ) Tj 1.730556 0 Td 53.472222 Tz (Such ) Tj 1.438889 0 Td 61.934156 Tz (compounds ) Tj 3.480556 0 Td 49.691358 Tz (are ) Tj 51.428571 0 0 51.428571 0 1702.129187 Tm 6.358333 0 Td 50.771605 Tz (non-limiting ) Tj 3.791667 0 Td 45.37037 Tz (in ) Tj 0.738889 0 Td 49.691358 Tz (nature ) Tj 1.905556 0 Td 59.41358 Tz (and ) Tj 1.205556 0 Td 49.691358 Tz (are ) Tj 1.030556 0 Td 50.231481 Tz (thus ) Tj 1.380556 0 Td 47.314815 Tz (indicative ) Tj 2.975 0 Td 55.092593 Tz (of ) Tj 0.738889 0 Td 49.691358 Tz (the ) Tj 1.030556 0 Td 50.05144 Tz (preferred ) Tj 40 0 0 40 0 1666 Tm 8.175 0 Td 76.136364 Tz (embodiments ) Tj 5.3 0 Td 72.916667 Tz (of ) Tj 0.975 0 Td 56.25 Tz (this ) Tj 1.625 0 Td 60.833333 Tz (invention. ) Tj 52.857143 0 0 52.857143 0 1617.224678 Tm 6.186486 0 Td 52.902903 Tz (Pipemidic ) Tj 3.008108 0 Td 56.756757 Tz (Acid ) Tj 1.57027 0 Td 48.558559 Tz (Derivative ) Tj 3.083784 0 Td 52.342342 Tz (Production ) Tj 51.428571 0 0 51.428571 0 1578.554202 Tm 7.097222 0 Td 62.654321 Tz (The ) Tj 1.205556 0 Td 51.388889 Tz (general ) Tj 2.275 0 Td 54.012346 Tz (procedure ) Tj 3.013889 0 Td 49.691358 Tz (for ) Tj 0.972222 0 Td 49.691358 Tz (the ) Tj 1.011111 0 Td 48.971193 Tz (synthesis ) Tj 2.761111 0 Td 53.472222 Tz (of ) Tj 0.719444 0 Td 55.092593 Tz (such ) Tj 1.419444 0 Td 50.968013 Tz (prospective ) Tj 51.428571 0 0 51.428571 0 1534.345178 Tm 6.358333 0 Td 78.858025 Tz (ATX ) Tj 1.672222 0 Td 46.342593 Tz (inhibitors ) Tj 3.072222 0 Td 60.493827 Tz (was ) Tj 1.341667 0 Td 51.851852 Tz (as ) Tj 0.913889 0 Td 50.925926 Tz (follows ) Tj 2.411111 0 Td 54.282407 Tz (\(and ) Tj 1.575 0 Td 61.574074 Tz (more ) Tj 1.730556 0 Td 45.910494 Tz (specifically ) Tj 3.558333 0 Td 65.895062 Tz (pre ) Tj 51.428571 0 0 51.428571 0 1492.279846 Tm 6.377778 0 Td 51.311728 Tz (sented ) Tj 2.119444 0 Td 50.771605 Tz (within ) Tj 2.080556 0 Td 49.691358 Tz (the ) Tj 1.205556 0 Td 58.333333 Tz (Examples ) Tj 3.072222 0 Td 51.851852 Tz (below\): ) Tj 2.411111 0 Td 61.574074 Tz (To ) Tj 1.030556 0 Td 51.851852 Tz (a ) Tj 0.602778 0 Td 48.206019 Tz (solution ) Tj 2.566667 0 Td 59.953704 Tz (of ) Tj 0.836111 0 Td 63.194444 Tz (pipe ) Tj 51.428571 0 0 51.428571 0 1452.609168 Tm 6.358333 0 Td 54.444444 Tz (midic ) Tj 1.808333 0 Td 50.231481 Tz (acid ) Tj 1.380556 0 Td 42.12963 Tz (in ) Tj 0.680556 0 Td 57.716049 Tz (N,N-dimethylformamide ) Tj 7.427778 0 Td 42.12963 Tz (\(1 ) Tj 0.758333 0 Td 68.055556 Tz (mL\) ) Tj 1.361111 0 Td 62.654321 Tz (was ) Tj 1.263889 0 Td 58.333333 Tz (added ) Tj 1.905556 0 Td 49.691358 Tz (the ) Tj 51.428571 0 0 51.428571 0 1412.32342 Tm 6.358333 0 Td 53.347578 Tz (corresponding ) Tj 4.511111 0 Td 47.727273 Tz (Substituted ) Tj 3.480556 0 Td 54.012346 Tz (phenyl ) Tj 2.313889 0 Td 48.179012 Tz (isothiocyanate. ) Tj 4.725 0 Td 45.37037 Tz (In ) Tj 0.894444 0 Td 64.814815 Tz (some ) Tj 51.428571 0 0 51.428571 0 1368.733333 Tm 6.358333 0 Td 46.990741 Tz (cases, ) Tj 1.827778 0 Td 50.106838 Tz (triethylamine ) Tj 4.044444 0 Td 61.574074 Tz (was ) Tj 1.244444 0 Td 58.333333 Tz (added ) Tj 1.866667 0 Td 46.990741 Tz (to ) Tj 0.7 0 Td 55.740741 Tz (speed ) Tj 1.769444 0 Td 50.771605 Tz (the ) Tj 1.05 0 Td 46.450617 Tz (reaction, ) Tj 2.644444 0 Td 54.444444 Tz (while ) Tj 1.769444 0 Td 48.611111 Tz (in ) Tj 48.571429 0 0 48.571429 0 1326 Tm 6.732353 0 Td 49.509804 Tz (others, ) Tj 2.470588 0 Td 51.470588 Tz (the ) Tj 1.255882 0 Td 52.757353 Tz (addition ) Tj 2.944118 0 Td 58.333333 Tz (of ) Tj 1.008824 0 Td 44.607843 Tz (this ) Tj 1.441176 0 Td 57.47549 Tz (base ) Tj 1.770588 0 Td 51.470588 Tz (led ) Tj 1.276471 0 Td 49.754902 Tz (to ) Tj 0.967647 0 Td 52.614379 Tz (the ) Tj 1.317647 0 Td 56.045752 Tz (formation ) Tj 3.417647 0 Td 60.04902 Tz (of ) Tj 51.428571 0 0 51.428571 0 1283.816774 Tm 6.338889 0 Td 51.851852 Tz (byproducts, ) Tj 3.733333 0 Td 59.41358 Tz (and ) Tj 1.380556 0 Td 60.493827 Tz (was ) Tj 1.4 0 Td 51.041667 Tz (thus ) Tj 1.516667 0 Td 51.041667 Tz (avoided. ) Tj 2.761111 0 Td 63.734568 Tz (The ) Tj 1.458333 0 Td 53.703704 Tz (mixture ) Tj 2.566667 0 Td 61.574074 Tz (was ) Tj 1.4 0 Td 54.282407 Tz (then ) Tj 51.428571 0 0 51.428571 0 1245.304762 Tm 6.358333 0 Td 54.62963 Tz (allowed ) Tj 2.430556 0 Td 45.37037 Tz (to ) Tj 0.7 0 Td 38.888889 Tz (stir ) Tj 1.05 0 Td 46.990741 Tz (at ) Tj 0.680556 0 Td 63.194444 Tz (room ) Tj 1.672222 0 Td 53.030303 Tz (temperature ) Tj 3.616667 0 Td 56.388889 Tz (under ) Tj 1.827778 0 Td 49.826389 Tz (nitrogen ) Tj 2.566667 0 Td 48.287037 Tz (overnight. ) Tj 40 0 0 40 0 1207 Tm 8.175 0 Td 81.944444 Tz (The ) Tj 1.725 0 Td 63.690476 Tz (solvent ) Tj 2.9 0 Td 80.555556 Tz (was ) Tj 1.7 0 Td 66.666667 Tz (then ) Tj 1.875 0 Td 76.785714 Tz (removed ) Tj 3.475 0 Td 58.333333 Tz (in ) Tj 0.95 0 Td 73.333333 Tz (vacuo ) Tj 2.425 0 Td 77.777778 Tz (and ) Tj 1.65 0 Td 62.5 Tz (the ) Tj 1.4 0 Td 63.690476 Tz (residue ) Tj 2.925 0 Td 79.166667 Tz (was ) Tj 51.428571 0 0 51.428571 0 1160.669891 Tm 6.358333 0 Td 49.331276 Tz (extracted ) Tj 2.819444 0 Td 53.796296 Tz (twice ) Tj 1.788889 0 Td 53.472222 Tz (with ) Tj 1.516667 0 Td 55.452675 Tz (methylene ) Tj 3.188889 0 Td 49.826389 Tz (chloride ) Tj 2.586111 0 Td 57.523148 Tz (from ) Tj 1.575 0 Td 56.481481 Tz (aqueous ) Tj 2.605556 0 Td 57.523148 Tz (Satu ) Tj 51.428571 0 0 51.428571 0 1118.025575 Tm 6.358333 0 Td 48.611111 Tz (rated ) Tj 1.75 0 Td 68.865741 Tz (ammonium ) Tj 3.655556 0 Td 46.8107 Tz (chloride. ) Tj 2.838889 0 Td 64.814815 Tz (The ) Tj 1.497222 0 Td 50.462963 Tz (organic ) Tj 2.45 0 Td 48.070988 Tz (layers ) Tj 2.080556 0 Td 58.333333 Tz (were ) Tj 1.691667 0 Td 83.179012 Tz (com ) Tj 51.428571 0 0 51.428571 0 1076.712846 Tm 6.338889 0 Td 50.231481 Tz (bined, ) Tj 2.119444 0 Td 49.259259 Tz (dried ) Tj 1.769444 0 Td 53.472222 Tz (with ) Tj 1.594444 0 Td 61.213992 Tz (magnesium ) Tj 3.616667 0 Td 44.155093 Tz (sulfate, ) Tj 2.411111 0 Td 42.939815 Tz (filtered ) Tj 2.313889 0 Td 60.493827 Tz (and ) Tj 1.361111 0 Td 63.734568 Tz (concen ) Tj 51.428571 0 0 51.428571 0 1036.869723 Tm 6.338889 0 Td 43.981481 Tz (trated. ) Tj 1.983333 0 Td 63.734568 Tz (The ) Tj 1.322222 0 Td 46.8107 Tz (resulting ) Tj 2.663889 0 Td 54.444444 Tz (crude ) Tj 1.769444 0 Td 53.703704 Tz (product ) Tj 2.411111 0 Td 60.493827 Tz (was ) Tj 1.283333 0 Td 50.231481 Tz (then ) Tj 1.361111 0 Td 47.800926 Tz (purified ) Tj 2.430556 0 Td 59.953704 Tz (by ) Tj 0.894444 0 Td 46.666667 Tz (flash ) Tj 51.428571 0 0 51.428571 0 994.82017 Tm 6.358333 0 Td 56.481481 Tz (chromatography ) Tj 4.919444 0 Td 59.953704 Tz (on ) Tj 0.913889 0 Td 42.12963 Tz (silica ) Tj 1.672222 0 Td 48.611111 Tz (gel ) Tj 1.05 0 Td 48.148148 Tz (eluting ) Tj 2.177778 0 Td 53.472222 Tz (with ) Tj 1.477778 0 Td 55.497685 Tz (methanol ) Tj 2.858333 0 Td 43.75 Tz (in ) Tj 0.738889 0 Td 68.865741 Tz (meth ) Tj 51.428571 0 0 51.428571 0 953.656863 Tm 6.338889 0 Td 53.796296 Tz (ylene ) Tj 1.827778 0 Td 49.826389 Tz (chloride ) Tj 2.644444 0 Td 56.944444 Tz (\(0-20%\) ) Tj 2.625 0 Td 46.990741 Tz (to ) Tj 0.777778 0 Td 49.259259 Tz (yield ) Tj 1.711111 0 Td 49.691358 Tz (the ) Tj 1.127778 0 Td 53.347578 Tz (corresponding ) Tj 4.413889 0 Td 49.421296 Tz (thiourea ) Tj 51.428571 0 0 51.428571 0 912.405648 Tm 6.358333 0 Td 49.331276 Tz (products. ) Tj 3.013889 0 Td 67.650463 Tz (Compound ) Tj 3.538889 0 Td 48.070988 Tz (purity ) Tj 2.1 0 Td 61.574074 Tz (was ) Tj 1.419444 0 Td 51.49177 Tz (evaluated ) Tj 3.111111 0 Td 58.333333 Tz (by ) Tj 1.088889 0 Td 75.347222 Tz (HPLC ) Tj 2.119444 0 Td 61.574074 Tz (and ) Tj 51.428571 0 0 51.428571 0 869.871795 Tm 6.358333 0 Td 51.851852 Tz (products ) Tj 2.702778 0 Td 58.333333 Tz (were ) Tj 1.594444 0 Td 54.444444 Tz (determined ) Tj 3.461111 0 Td 43.75 Tz (to ) Tj 0.719444 0 Td 58.333333 Tz (be ) Tj 0.913889 0 Td 78.587963 Tz (295% ) Tj 2.061111 0 Td 44.444444 Tz (purity. ) Tj 51.428571 0 0 51.428571 0 795.333333 Tm 13.552778 0 Td 61.111111 Tz (Example ) Tj 2.8 0 Td 38.888889 Tz (1 ) Tj 51.428571 0 0 51.428571 0 708.06422 Tm 6.377778 0 Td 59.953704 Tz (Lead ) Tj 1.613889 0 Td 67.650463 Tz (Compound ) Tj 3.383333 0 Td 87.5 Tz (A ) Tj 0.719444 0 Td 57.523148 Tz (from ) Tj 1.575 0 Td 52.391975 Tz (above. ) Tj 51.428571 0 0 51.428571 0 633.04 Tm 13.552778 0 Td 61.111111 Tz (Example ) Tj 2.741667 0 Td 58.333333 Tz (2 ) Tj 57.142857 0 0 57.142857 0 549 Tm 6.895 0 Td 51.821705 Tz (2-\(4-\(4-dimethylaminonapthylphenyl\)aminocar ) Tj 57.142857 0 0 57.142857 0 508 Tm 6.8075 0 Td 46.970486 Tz (bonothioyl-1-piperazinyl\)-8-ethyl-5-oxo-5,8-dihy ) Tj 51.428571 0 0 51.428571 0 465.796062 Tm 7.894444 0 Td 53.292181 Tz (dropyrido ) Tj 3.111111 0 Td 50.957854 Tz (2,3-dipyrimidine-6-carboxylic ) Tj 9.022222 0 Td 51.851852 Tz (acid ) Tj 1.419444 0 Td 46.450617 Tz (\(2\) ) Tj 51.428571 0 0 51.428571 0 380.79597 Tm 7.116667 0 Td 54.372428 Tz (Pipemidic ) Tj 3.091667 0 Td 51.041667 Tz (acid ) Tj 1.419444 0 Td 52.932099 Tz (\(25 ) Tj 1.186111 0 Td 59.41358 Tz (mg, ) Tj 1.283333 0 Td 54.012346 Tz (0.0824 ) Tj 2.216667 0 Td 57.253086 Tz (mmol\), ) Tj 2.255556 0 Td 58.333333 Tz (4-dimethylamino ) Tj 51.428571 0 0 51.428571 0 339.862559 Tm 6.436111 0 Td 50.020129 Tz (1-napthylisothiocyanate ) Tj 7.038889 0 Td 49.259259 Tz (\(18.8 ) Tj 1.633333 0 Td 77.777778 Tz (mg ) Tj 1.225 0 Td 55.092593 Tz (0.0824 ) Tj 2.158333 0 Td 63.518519 Tz (mmol\) ) Tj 2.002778 0 Td 59.41358 Tz (and ) Tj 1.186111 0 Td 50.925926 Tz (triethy ) Tj 51.428571 0 0 51.428571 0 293 Tm 6.358333 0 Td 55.632716 Tz (lamine ) Tj 2.158333 0 Td 50.771605 Tz (\(23 ) Tj 1.127778 0 Td 52.932099 Tz (uL, ) Tj 1.108333 0 Td 54.444444 Tz (0.165 ) Tj 1.827778 0 Td 63.518519 Tz (mmol\) ) Tj 2.080556 0 Td 58.333333 Tz (were ) Tj 1.555556 0 Td 48.611111 Tz (used. ) Tj 1.672222 0 Td 46.720679 Tz (Purification ) Tj 3.5 0 Td 59.953704 Tz (on ) Tj 0.894444 0 Td 43.209877 Tz (silica ) Tj 58.571429 0 0 58.571429 0 254.924 Tm 5.565854 0 Td 45.528455 Tz (yielded ) Tj 2.15122 0 Td 56.554878 Tz (compound ) Tj 2.936585 0 Td 54.065041 Tz (2 ) Tj 0.580488 0 Td 39.837398 Tz (in ) Tj 0.7 0 Td 47.804878 Tz (Table ) Tj 1.707317 0 Td 34.146341 Tz (1, ) Tj 0.64878 0 Td 51.788618 Tz (below ) Tj 1.809756 0 Td 45.528455 Tz (\(23 ) Tj 1.109756 0 Td 53.116531 Tz (mg, ) Tj 1.212195 0 Td 51.219512 Tz (53%\). ) Tj 1.826829 0 Td 55.487805 Tz ("H ) Tj 51.428571 0 0 51.428571 0 210 Tm 6.358333 0 Td 92.901235 Tz (NMR ) Tj 1.847222 0 Td 55.902778 Tz (\(300 ) Tj 1.555556 0 Td 68.865741 Tz (MHz, ) Tj 1.866667 0 Td 73.240741 Tz (CDC1\) ) Tj 2.411111 0 Td 51.851852 Tz (& ) Tj 0.544444 0 Td 51.041667 Tz (9.29 ) Tj 1.477778 0 Td 36.728395 Tz (\(s, ) Tj 0.913889 0 Td 52.662037 Tz (1H\), ) Tj 1.458333 0 Td 52.662037 Tz (8.63 ) Tj 1.497222 0 Td 36.728395 Tz (\(s, ) Tj 0.933333 0 Td 51.851852 Tz (1H\), ) Tj 1.438889 0 Td 63.194444 Tz (8.32 ) Tj 51.428571 0 0 51.428571 0 168 Tm 6.377778 0 Td 52.662037 Tz (8.24 ) Tj 1.438889 0 Td 52.932099 Tz (\(m, ) Tj 1.186111 0 Td 52.662037 Tz (1H\), ) Tj 1.419444 0 Td 51.131687 Tz (8.02-7.93 ) Tj 2.975 0 Td 52.932099 Tz (\(m. ) Tj 1.205556 0 Td 51.851852 Tz (1H\), ) Tj 1.419444 0 Td 51.131687 Tz (7.62-7.46 ) Tj 2.936111 0 Td 55.092593 Tz (\(m, ) Tj 1.147222 0 Td 55.092593 Tz (3H\), ) Tj 1.497222 0 Td 51.851852 Tz (7.02 ) Tj 1.438889 0 Td 42.12963 Tz (\(d. ) Tj 30 0 0 30 0 2547 Tm 41.666667 0 Td 75 Tz (10 ) Tj 30 0 0 30 0 2339 Tm 41.666667 0 Td 72.222222 Tz (15 ) Tj 30 0 0 30 0 1923 Tm 41.6 0 Td 77.777778 Tz (25 ) Tj 30 0 0 30 0 1716 Tm 41.6 0 Td 80.555556 Tz (30 ) Tj 30 0 0 30 0 1507 Tm 41.6 0 Td 77.777778 Tz (35 ) Tj 30 0 0 30 0 1299 Tm 41.566667 0 Td 83.333333 Tz (40 ) Tj 30 0 0 30 0 1091 Tm 41.566667 0 Td 80.555556 Tz (45 ) Tj 30 0 0 30 0 883 Tm 41.6 0 Td 80.555556 Tz (50 ) Tj 30 0 0 30 0 675 Tm 41.6 0 Td 77.777778 Tz (55 ) Tj 30 0 0 30 0 467 Tm 41.633333 0 Td 77.777778 Tz (60 ) Tj 30 0 0 30 0 259 Tm 41.633333 0 Td 75 Tz (65 ) Tj 51.428571 0 0 51.428571 0 2969 Tm 33.6 0 Td 74.537037 Tz (14 ) Tj 51.428571 0 0 51.428571 0 2913.401506 Tm 25.297222 0 Td 53.472222 Tz (J7.95 ) Tj 2.177778 0 Td 54.012346 Tz (Hz, ) Tj 1.225 0 Td 51.851852 Tz (1H\), ) Tj 1.419444 0 Td 52.662037 Tz (4.29 ) Tj 1.438889 0 Td 43.209877 Tz (\(q, ) Tj 0.933333 0 Td 55.632716 Tz (J=6.90 ) Tj 2.197222 0 Td 55.092593 Tz (Hz, ) Tj 1.166667 0 Td 53.472222 Tz (2H\), ) Tj 1.477778 0 Td 51.49177 Tz (4.16-3.85 ) Tj 2.955556 0 Td 54.012346 Tz (\(m, ) Tj 1.166667 0 Td 53.472222 Tz (8H\), ) Tj 51.428571 0 0 51.428571 0 2875.111111 Tm 25.297222 0 Td 53.472222 Tz (2.90 ) Tj 1.458333 0 Td 37.808642 Tz (\(s, ) Tj 0.913889 0 Td 53.472222 Tz (6H\), ) Tj 1.536111 0 Td 48.611111 Tz (1.45 ) Tj 1.4 0 Td 32.407407 Tz (\(t, ) Tj 0.797222 0 Td 54.552469 Tz (J7.08 ) Tj 2.197222 0 Td 52.932099 Tz (Hz, ) Tj 1.166667 0 Td 62.654321 Tz (3H\) ) Tj 1.302778 0 Td 60.763889 Tz (ppm. ) Tj 51.428571 0 0 51.428571 0 2804.093333 Tm 32.472222 0 Td 61.574074 Tz (Example ) Tj 2.761111 0 Td 55.092593 Tz (3 ) Tj 57.142857 0 0 57.142857 0 2725 Tm 23.695 0 Td 51.333333 Tz (2-\(4-\(4-iodophenyl\)aminocarbonothioyl-1-piper ) Tj 51.428571 0 0 51.428571 0 2686 Tm 26.425 0 Td 51.719577 Tz (azinyl\)-8-ethyl-5-oxo-5,8-dihydropyrido2,3-dipyri ) Tj 51.428571 0 0 51.428571 0 2644.931707 Tm 29.847222 0 Td 51.851852 Tz (midine-6-carboxylic ) Tj 6.105556 0 Td 51.041667 Tz (acid ) Tj 1.419444 0 Td 46.450617 Tz (\(3\) ) Tj 51.428571 0 0 51.428571 0 2564.436975 Tm 26.036111 0 Td 54.372428 Tz (Pipemidic ) Tj 3.363889 0 Td 50.231481 Tz (acid ) Tj 1.613889 0 Td 51.851852 Tz (\(25 ) Tj 1.419444 0 Td 76.157407 Tz (mg ) Tj 1.516667 0 Td 55.092593 Tz (0.0824 ) Tj 2.430556 0 Td 57.253086 Tz (mmol\), ) Tj 2.527778 0 Td 53.472222 Tz (4-iodophenyl ) Tj 51.428571 0 0 51.428571 0 2524.440281 Tm 25.297222 0 Td 50.231481 Tz (isothiocyanate ) Tj 4.316667 0 Td 49.907407 Tz (\(21.5 ) Tj 1.633333 0 Td 59.41358 Tz (mg, ) Tj 1.225 0 Td 55.092593 Tz (0.0824 ) Tj 2.119444 0 Td 64.814815 Tz (mmol\) ) Tj 2.041667 0 Td 58.333333 Tz (and ) Tj 1.147222 0 Td 50.356125 Tz (triethylamine ) Tj 4.025 0 Td 50.771605 Tz (\(23 ) Tj 51.428571 0 0 51.428571 0 2482.156129 Tm 25.355556 0 Td 51.851852 Tz (uL, ) Tj 1.225 0 Td 53.148148 Tz (0.165 ) Tj 1.925 0 Td 63.518519 Tz (mmol\) ) Tj 2.197222 0 Td 58.333333 Tz (were ) Tj 1.652778 0 Td 49.907407 Tz (used. ) Tj 1.827778 0 Td 46.450617 Tz (Purification ) Tj 3.636111 0 Td 59.953704 Tz (on ) Tj 1.011111 0 Td 41.589506 Tz (silica ) Tj 1.769444 0 Td 51.851852 Tz (yielded ) Tj 58.571429 0 0 58.571429 0 2443.438931 Tm 22.212195 0 Td 55.843496 Tz (compound ) Tj 2.85122 0 Td 48.373984 Tz (3 ) Tj 0.495122 0 Td 39.837398 Tz (in ) Tj 0.597561 0 Td 47.804878 Tz (Table ) Tj 1.639024 0 Td 32.723577 Tz (1, ) Tj 0.580488 0 Td 50.650407 Tz (below ) Tj 1.707317 0 Td 46.476965 Tz (\(36 ) Tj 1.007317 0 Td 53.116531 Tz (mg, ) Tj 1.109756 0 Td 51.219512 Tz (77%\). ) Tj 1.741463 0 Td 55.487805 Tz ("H ) Tj 0.819512 0 Td 81.571816 Tz (NMR ) Tj 1.621951 0 Td 48.373984 Tz (\(300 ) Tj 51.428571 0 0 51.428571 0 2402 Tm 25.297222 0 Td 69.675926 Tz (MHz, ) Tj 1.808333 0 Td 73.888889 Tz (CDC1\) ) Tj 2.372222 0 Td 57.037037 Tz (89.32 ) Tj 1.866667 0 Td 38.888889 Tz (\(s, ) Tj 0.894444 0 Td 51.851852 Tz (1H\), ) Tj 1.380556 0 Td 53.472222 Tz (8.66 ) Tj 1.419444 0 Td 37.808642 Tz (\(s, ) Tj 0.913889 0 Td 51.041667 Tz (1H\), ) Tj 1.380556 0 Td 52.662037 Tz (7.66 ) Tj 1.4 0 Td 39.969136 Tz (\(d. ) Tj 0.875 0 Td 55.632716 Tz (J=6.94 ) Tj 2.177778 0 Td 52.932099 Tz (Hz, ) Tj 51.428571 0 0 51.428571 0 2362 Tm 25.355556 0 Td 51.851852 Tz (1H\), ) Tj 1.438889 0 Td 51.041667 Tz (7.37 ) Tj 1.419444 0 Td 36.728395 Tz (\(s, ) Tj 0.894444 0 Td 52.662037 Tz (1H\), ) Tj 1.458333 0 Td 52.662037 Tz (7.27 ) Tj 1.419444 0 Td 36.728395 Tz (\(s, ) Tj 0.894444 0 Td 52.662037 Tz (1H\), ) Tj 1.458333 0 Td 52.662037 Tz (7.00 ) Tj 1.419444 0 Td 41.049383 Tz (\(d. ) Tj 0.933333 0 Td 55.092593 Tz (J=7.44 ) Tj 2.158333 0 Td 55.092593 Tz (Hz, ) Tj 1.225 0 Td 51.041667 Tz (1H\), ) Tj 1.419444 0 Td 51.041667 Tz (4.33 ) Tj 51.428571 0 0 51.428571 0 2323.363636 Tm 25.316667 0 Td 41.049383 Tz (\(q, ) Tj 0.875 0 Td 55.092593 Tz (J=6.90 ) Tj 2.119444 0 Td 55.092593 Tz (Hz, ) Tj 1.108333 0 Td 54.282407 Tz (2H\), ) Tj 1.419444 0 Td 51.851852 Tz (4.21-3.99 ) Tj 2.936111 0 Td 56.944444 Tz (\(m,8H\), ) Tj 2.566667 0 Td 51.041667 Tz (1.49 ) Tj 1.322222 0 Td 34.567901 Tz (\(t, ) Tj 0.738889 0 Td 55.092593 Tz (J=7.14 ) Tj 2.138889 0 Td 61.574074 Tz (Hz,3H\) ) Tj 51.428571 0 0 51.428571 0 2213.046358 Tm 32.472222 0 Td 61.574074 Tz (Example ) Tj 2.761111 0 Td 58.333333 Tz (4 ) Tj 57.142857 0 0 57.142857 0 2134 Tm 23.905 0 Td 49.777778 Tz (2-\(4-\(4-carboxylphenyl\)aminocarbonothioyl\)-1- ) Tj 51.428571 0 0 51.428571 0 2095.171691 Tm 26.386111 0 Td 50.378788 Tz (piperazinyl\)-8-ethyl-5-oxo-5,8-dihydropyrido ) Tj 13.533333 0 Td 51.203704 Tz (2,3-d ) Tj 51.428571 0 0 51.428571 0 2054.199575 Tm 29.263889 0 Td 51.429147 Tz (pyrimidine-6-carboxylic ) Tj 7.272222 0 Td 51.041667 Tz (acid ) Tj 1.419444 0 Td 46.450617 Tz (\(4\) ) Tj 51.428571 0 0 51.428571 0 1973.724005 Tm 26.036111 0 Td 54.372428 Tz (Pipemidic ) Tj 3.130556 0 Td 51.851852 Tz (acid ) Tj 1.477778 0 Td 51.851852 Tz (\(25 ) Tj 1.166667 0 Td 77.777778 Tz (mg ) Tj 1.341667 0 Td 54.552469 Tz (0.0824 ) Tj 2.236111 0 Td 57.253086 Tz (mmol\), ) Tj 2.294444 0 Td 52.864583 Tz (4-isothiocyanato ) Tj 51.428571 0 0 51.428571 0 1932.5 Tm 25.277778 0 Td 54.166667 Tz (benzoic ) Tj 2.45 0 Td 51.851852 Tz (acid ) Tj 1.438889 0 Td 49.259259 Tz (\(14.8 ) Tj 1.730556 0 Td 59.41358 Tz (mg, ) Tj 1.263889 0 Td 55.092593 Tz (0.0824 ) Tj 2.216667 0 Td 64.166667 Tz (mmol\) ) Tj 2.080556 0 Td 60.493827 Tz (and ) Tj 1.263889 0 Td 49.85755 Tz (triethylamine ) Tj 4.083333 0 Td 50.771605 Tz (\(23 ) Tj 51.428571 0 0 51.428571 0 1891.156129 Tm 25.355556 0 Td 51.851852 Tz (uL, ) Tj 1.225 0 Td 53.148148 Tz (0.165 ) Tj 1.925 0 Td 63.518519 Tz (mmol\) ) Tj 2.197222 0 Td 58.333333 Tz (were ) Tj 1.652778 0 Td 49.907407 Tz (used. ) Tj 1.827778 0 Td 46.450617 Tz (Purification ) Tj 3.636111 0 Td 59.953704 Tz (on ) Tj 1.011111 0 Td 41.589506 Tz (silica ) Tj 1.769444 0 Td 51.851852 Tz (yielded ) Tj 58.571429 0 0 58.571429 0 1853.438931 Tm 22.212195 0 Td 55.843496 Tz (compound ) Tj 2.85122 0 Td 54.065041 Tz (4 ) Tj 0.495122 0 Td 39.837398 Tz (in ) Tj 0.597561 0 Td 47.804878 Tz (Table ) Tj 1.639024 0 Td 32.723577 Tz (1, ) Tj 0.580488 0 Td 50.650407 Tz (below ) Tj 1.707317 0 Td 44.579946 Tz (\(23 ) Tj 1.007317 0 Td 53.116531 Tz (mg, ) Tj 1.109756 0 Td 51.219512 Tz (58%\). ) Tj 1.741463 0 Td 55.487805 Tz ("H ) Tj 0.819512 0 Td 81.571816 Tz (NMR ) Tj 1.621951 0 Td 48.373984 Tz (\(300 ) Tj 51.428571 0 0 51.428571 0 1811 Tm 25.297222 0 Td 69.675926 Tz (MHz, ) Tj 1.847222 0 Td 77.777778 Tz (DMSO\) ) Tj 2.527778 0 Td 51.851852 Tz (& ) Tj 0.486111 0 Td 50.231481 Tz (9.71 ) Tj 1.438889 0 Td 38.888889 Tz (\(s, ) Tj 0.913889 0 Td 52.662037 Tz (1H\), ) Tj 1.419444 0 Td 53.472222 Tz (9.24 ) Tj 1.438889 0 Td 38.888889 Tz (\(s, ) Tj 0.933333 0 Td 51.851852 Tz (1H\), ) Tj 1.4 0 Td 52.662037 Tz (8.98 ) Tj 1.458333 0 Td 37.808642 Tz (\(s, ) Tj 0.894444 0 Td 52.662037 Tz (1H\), ) Tj 1.438889 0 Td 51.851852 Tz (7.87 ) Tj 51.428571 0 0 51.428571 0 1772 Tm 25.316667 0 Td 39.969136 Tz (\(d. ) Tj 0.991667 0 Td 53.472222 Tz (J=8.53 ) Tj 2.216667 0 Td 55.092593 Tz (Hz, ) Tj 1.205556 0 Td 55.092593 Tz (2H\), ) Tj 1.575 0 Td 51.851852 Tz (7.49 ) Tj 1.497222 0 Td 39.969136 Tz (\(d. ) Tj 0.972222 0 Td 54.012346 Tz (J=8.43 ) Tj 2.236111 0 Td 55.092593 Tz (Hz, ) Tj 1.186111 0 Td 55.902778 Tz (2H\), ) Tj 1.555556 0 Td 51.851852 Tz (4.45-4.39 ) Tj 3.033333 0 Td 52.932099 Tz (\(m, ) Tj 51.428571 0 0 51.428571 0 1732.85592 Tm 25.297222 0 Td 54.282407 Tz (2H\), ) Tj 1.477778 0 Td 51.49177 Tz (4.10-4.03 ) Tj 3.013889 0 Td 51.851852 Tz (\(m, ) Tj 1.147222 0 Td 53.472222 Tz (8H\), ) Tj 1.555556 0 Td 51.041667 Tz (1.38 ) Tj 1.4 0 Td 33.487654 Tz (\(t, ) Tj 0.797222 0 Td 54.552469 Tz (J=6.94 ) Tj 2.216667 0 Td 51.851852 Tz (Hz, ) Tj 1.147222 0 Td 63.734568 Tz (3H\) ) Tj 1.302778 0 Td 60.763889 Tz (ppm. ) Tj 51.428571 0 0 51.428571 0 1663.093333 Tm 32.472222 0 Td 61.574074 Tz (Example ) Tj 2.761111 0 Td 55.092593 Tz (5 ) Tj 57.142857 0 0 57.142857 0 1583 Tm 23.8 0 Td 51.704545 Tz (2-\(4-\(2-methylesterphenyl\)aminocarbonothioyl ) Tj 51.428571 0 0 51.428571 0 1544 Tm 26.463889 0 Td 50.685185 Tz (1-piperazinyl\)-8-ethyl-5-oxo-5,8-dihydropyrido2.3- ) Tj 51.428571 0 0 51.428571 0 1503.310757 Tm 28.952778 0 Td 53.472222 Tz (dpyrimidine-6-carboxylic ) Tj 7.875 0 Td 51.041667 Tz (acid ) Tj 1.419444 0 Td 46.450617 Tz (\(5\) ) Tj 51.428571 0 0 51.428571 0 1421.181347 Tm 26.036111 0 Td 54.372428 Tz (Pipemidic ) Tj 3.130556 0 Td 51.851852 Tz (acid ) Tj 1.477778 0 Td 51.851852 Tz (\(25 ) Tj 1.186111 0 Td 59.41358 Tz (mg, ) Tj 1.322222 0 Td 54.552469 Tz (0.0824 ) Tj 2.236111 0 Td 57.79321 Tz (mmol\), ) Tj 2.333333 0 Td 54.552469 Tz (methyl ) Tj 2.216667 0 Td 52.211934 Tz (2-isothio ) Tj 51.428571 0 0 51.428571 0 1382.980198 Tm 25.297222 0 Td 53.580247 Tz (cyanatobenzoate ) Tj 5.133333 0 Td 51.851852 Tz (\(16 ) Tj 1.263889 0 Td 59.41358 Tz (mg, ) Tj 1.380556 0 Td 55.092593 Tz (0.0824 ) Tj 2.275 0 Td 64.814815 Tz (mmol\) ) Tj 2.197222 0 Td 59.41358 Tz (and ) Tj 1.341667 0 Td 49.85755 Tz (triethylamine ) Tj 51.428571 0 0 51.428571 0 1340.0887 Tm 25.316667 0 Td 50.771605 Tz (\(23 ) Tj 1.147222 0 Td 50.771605 Tz (uL, ) Tj 1.05 0 Td 54.444444 Tz (0.165 ) Tj 1.808333 0 Td 63.518519 Tz (mmol\) ) Tj 2.061111 0 Td 58.333333 Tz (were ) Tj 1.555556 0 Td 48.611111 Tz (used. ) Tj 1.633333 0 Td 46.720679 Tz (Purification ) Tj 3.5 0 Td 61.574074 Tz (on ) Tj 0.894444 0 Td 41.589506 Tz (silica ) Tj 1.633333 0 Td 51.851852 Tz (yielded ) Tj 58.571429 0 0 58.571429 0 1301.438931 Tm 22.212195 0 Td 55.843496 Tz (compound ) Tj 2.868293 0 Td 48.373984 Tz (5 ) Tj 0.478049 0 Td 39.837398 Tz (in ) Tj 0.597561 0 Td 47.804878 Tz (Table ) Tj 1.639024 0 Td 32.723577 Tz (1, ) Tj 0.580488 0 Td 50.650407 Tz (below ) Tj 1.707317 0 Td 46.476965 Tz (\(24 ) Tj 1.007317 0 Td 53.116531 Tz (mg, ) Tj 1.109756 0 Td 51.219512 Tz (59%\). ) Tj 1.741463 0 Td 55.487805 Tz ("H ) Tj 0.819512 0 Td 81.571816 Tz (NMR ) Tj 1.621951 0 Td 48.373984 Tz (\(300 ) Tj 52.857143 0 0 52.857143 0 1259 Tm 24.613514 0 Td 67.792793 Tz (MHz, ) Tj 1.816216 0 Td 59.90991 Tz (CDC1,\) ) Tj 2.345946 0 Td 50.45045 Tz (& ) Tj 0.567568 0 Td 50.45045 Tz (11.14 ) Tj 1.702703 0 Td 36.786787 Tz (\(s, ) Tj 0.889189 0 Td 50.45045 Tz (1H\), ) Tj 1.381081 0 Td 51.238739 Tz (9.35 ) Tj 1.418919 0 Td 40.990991 Tz (\(d. ) Tj 0.927027 0 Td 53.603604 Tz (J=3.14 ) Tj 2.1 0 Td 54.654655 Tz (Hz, ) Tj 1.22973 0 Td 50.45045 Tz (1H\), ) Tj 1.362162 0 Td 51.238739 Tz (8.77 ) Tj 51.428571 0 0 51.428571 0 1220 Tm 25.316667 0 Td 38.888889 Tz (\(d. ) Tj 0.952778 0 Td 54.552469 Tz (J7.80 ) Tj 2.138889 0 Td 57.253086 Tz (Hz, ) Tj 1.263889 0 Td 51.041667 Tz (1H\), ) Tj 1.438889 0 Td 52.662037 Tz (8.69 ) Tj 1.477778 0 Td 39.969136 Tz (\(d. ) Tj 0.913889 0 Td 55.092593 Tz (J=2.99 ) Tj 2.197222 0 Td 55.092593 Tz (Hz, ) Tj 1.244444 0 Td 51.041667 Tz (1H\), ) Tj 1.419444 0 Td 50.231481 Tz (8.01 ) Tj 1.477778 0 Td 39.969136 Tz (\(d. ) Tj 0.952778 0 Td 53.472222 Tz (J=6.95 ) Tj 51.428571 0 0 51.428571 0 1181 Tm 25.297222 0 Td 57.253086 Tz (HZ, ) Tj 1.341667 0 Td 51.041667 Tz (1H\), ) Tj 1.516667 0 Td 51.041667 Tz (7.55 ) Tj 1.516667 0 Td 33.487654 Tz (\(t, ) Tj 0.855556 0 Td 54.012346 Tz (J=7.72 ) Tj 2.197222 0 Td 57.253086 Tz (Hz, ) Tj 1.322222 0 Td 52.662037 Tz (1H\), ) Tj 1.536111 0 Td 51.851852 Tz (7.12 ) Tj 1.516667 0 Td 32.407407 Tz (\(t, ) Tj 0.855556 0 Td 54.552469 Tz (J=7.99 ) Tj 2.216667 0 Td 57.253086 Tz (Hz, ) Tj 1.322222 0 Td 51.851852 Tz (1H\), ) Tj 51.428571 0 0 51.428571 0 1141.870588 Tm 25.297222 0 Td 51.49177 Tz (4.38-4.12 ) Tj 2.975 0 Td 51.851852 Tz (\(m. ) Tj 1.244444 0 Td 53.148148 Tz (10H\), ) Tj 1.788889 0 Td 51.851852 Tz (3.92 ) Tj 1.438889 0 Td 38.888889 Tz (\(s, ) Tj 0.894444 0 Td 53.472222 Tz (3H\), ) Tj 1.555556 0 Td 46.990741 Tz (1.51 ) Tj 1.4 0 Td 54.012346 Tz (\(m, ) Tj 1.147222 0 Td 63.734568 Tz (3H\) ) Tj 1.341667 0 Td 59.953704 Tz (ppm. ) Tj 51.428571 0 0 51.428571 0 1071.093333 Tm 32.472222 0 Td 61.574074 Tz (Example ) Tj 2.780556 0 Td 55.092593 Tz (6 ) Tj 57.142857 0 0 57.142857 0 992 Tm 23.6425 0 Td 51.722222 Tz (2-\(4-\(4-morpholinosulfonylphenyl\)aminocarbono ) Tj 57.142857 0 0 57.142857 0 953 Tm 23.7475 0 Td 46.72619 Tz (thioyl-1-piperazinyl\)-8-ethyl-5-oxo-5,8-dihydropy ) Tj 51.428571 0 0 51.428571 0 912.672986 Tm 27.669444 0 Td 51.851852 Tz (rido2,3-dipyrimidine-6-carboxylic ) Tj 10.461111 0 Td 51.041667 Tz (acid ) Tj 1.419444 0 Td 45.37037 Tz (\(6\) ) Tj 51.428571 0 0 51.428571 0 831.442186 Tm 26.036111 0 Td 54.372428 Tz (Pipemidic ) Tj 3.169444 0 Td 50.231481 Tz (acid ) Tj 1.438889 0 Td 49.907407 Tz (\(14.2 ) Tj 1.769444 0 Td 59.41358 Tz (mg, ) Tj 1.283333 0 Td 55.632716 Tz (0.0468 ) Tj 2.255556 0 Td 58.333333 Tz (mmol\), ) Tj 2.313889 0 Td 57.58547 Tz (4-\(morpholino ) Tj 51.428571 0 0 51.428571 0 792.987654 Tm 25.316667 0 Td 50.555556 Tz (sulfonyl\)phenyl ) Tj 4.841667 0 Td 50 Tz (isothiocyanate ) Tj 4.452778 0 Td 52.932099 Tz (\(14 ) Tj 1.263889 0 Td 44.560185 Tz (mg., ) Tj 1.380556 0 Td 54.552469 Tz (0.0468 ) Tj 2.255556 0 Td 64.814815 Tz (mmol\) ) Tj 2.197222 0 Td 59.41358 Tz (and ) Tj 51.428571 0 0 51.428571 0 747.968176 Tm 25.277778 0 Td 50.106838 Tz (triethylamine ) Tj 4.083333 0 Td 51.851852 Tz (\(13 ) Tj 1.225 0 Td 51.851852 Tz (uL, ) Tj 1.127778 0 Td 55.092593 Tz (0.0935 ) Tj 2.216667 0 Td 64.166667 Tz (mmol\) ) Tj 2.138889 0 Td 58.333333 Tz (were ) Tj 1.613889 0 Td 47.962963 Tz (used. ) Tj 1.730556 0 Td 46.720679 Tz (Purification ) Tj 57.142857 0 0 57.142857 0 706.90099 Tm 22.7675 0 Td 55.416667 Tz (on ) Tj 0.98 0 Td 37.916667 Tz (silica ) Tj 1.6275 0 Td 46.666667 Tz (yielded ) Tj 2.2925 0 Td 49.583333 Tz (6 ) Tj 0.6125 0 Td 48.611111 Tz (\(24 ) Tj 1.1725 0 Td 54.444444 Tz (mg. ) Tj 1.3125 0 Td 52.5 Tz (85%\). ) Tj 2.135 0 Td 78.75 Tz (H ) Tj 0.77 0 Td 84.583333 Tz (NMR ) Tj 1.82 0 Td 49.583333 Tz (\(300 ) Tj 1.505 0 Td 61.25 Tz (MHz, ) Tj 51.428571 0 0 51.428571 0 663 Tm 25.297222 0 Td 74.537037 Tz (CDC1\) ) Tj 2.508333 0 Td 48.611111 Tz (& ) Tj 0.563889 0 Td 53.472222 Tz (9.28 ) Tj 1.536111 0 Td 37.808642 Tz (\(s, ) Tj 1.011111 0 Td 50.231481 Tz (1H\), ) Tj 1.458333 0 Td 52.662037 Tz (8.65 ) Tj 1.536111 0 Td 38.888889 Tz (\(s, ) Tj 1.011111 0 Td 51.851852 Tz (1H\), ) Tj 1.497222 0 Td 53.472222 Tz (8.09 ) Tj 1.536111 0 Td 37.808642 Tz (\(s, ) Tj 1.011111 0 Td 50.231481 Tz (1H\), ) Tj 1.477778 0 Td 53.472222 Tz (7.64 ) Tj 1.555556 0 Td 41.049383 Tz (\(d. ) Tj 51.428571 0 0 51.428571 0 621 Tm 25.297222 0 Td 52.391975 Tz (J=8.71 ) Tj 2.158333 0 Td 54.012346 Tz (Hz, ) Tj 1.088889 0 Td 55.092593 Tz (2H\), ) Tj 1.477778 0 Td 48.611111 Tz (7.51 ) Tj 1.4 0 Td 41.049383 Tz (\(d. ) Tj 0.913889 0 Td 51.851852 Tz (J=8.61 ) Tj 2.138889 0 Td 54.012346 Tz (Hz, ) Tj 1.108333 0 Td 54.282407 Tz (2H\), ) Tj 1.458333 0 Td 50.05144 Tz (4.43-4.01 ) Tj 2.916667 0 Td 55.092593 Tz (\(m, ) Tj 1.186111 0 Td 53.148148 Tz (10H\), ) Tj 51.428571 0 0 51.428571 0 580 Tm 25.297222 0 Td 51.851852 Tz (3.80-3.70 ) Tj 2.936111 0 Td 52.932099 Tz (\(m, ) Tj 1.088889 0 Td 53.472222 Tz (4H\), ) Tj 1.419444 0 Td 51.851852 Tz (3.04-2.98 ) Tj 2.955556 0 Td 52.932099 Tz (\(m, ) Tj 1.088889 0 Td 55.092593 Tz (4H\), ) Tj 1.497222 0 Td 50.231481 Tz (1.49 ) Tj 1.341667 0 Td 33.487654 Tz (\(t, ) Tj 0.738889 0 Td 55.092593 Tz (J=7.17 ) Tj 2.119444 0 Td 56.17284 Tz (Hz, ) Tj 1.147222 0 Td 62.654321 Tz (3H\) ) Tj 51.428571 0 0 51.428571 0 466.046358 Tm 32.472222 0 Td 61.574074 Tz (Example ) Tj 2.761111 0 Td 58.333333 Tz (7 ) Tj 57.142857 0 0 57.142857 0 383 Tm 24.1675 0 Td 51.25 Tz (2-\(4-\(3-benzothiadiazolphenyl\)aminocarbono ) Tj 57.142857 0 0 57.142857 0 342 Tm 23.7475 0 Td 46.72619 Tz (thioyl-1-piperazinyl\)-8-ethyl-5-oxo-5,8-dihydropy ) Tj 51.428571 0 0 51.428571 0 299.672986 Tm 27.669444 0 Td 51.851852 Tz (rido2,3-dipyrimidine-6-carboxylic ) Tj 10.461111 0 Td 51.041667 Tz (acid ) Tj 1.419444 0 Td 45.37037 Tz (\(7\) ) Tj 51.428571 0 0 51.428571 0 212.017136 Tm 26.036111 0 Td 54.372428 Tz (Pipemidic ) Tj 3.052778 0 Td 51.041667 Tz (acid ) Tj 1.341667 0 Td 52.932099 Tz (\(25 ) Tj 1.108333 0 Td 59.41358 Tz (mg, ) Tj 1.205556 0 Td 55.092593 Tz (0.0824 ) Tj 2.158333 0 Td 57.79321 Tz (mmol\), ) Tj 2.216667 0 Td 52.211934 Tz (2,1,3-benzothiadia ) Tj 51.428571 0 0 51.428571 0 172.759124 Tm 25.297222 0 Td 47.395833 Tz (Zol-5-yl ) Tj 2.469444 0 Td 50 Tz (isothiocyanate ) Tj 4.394444 0 Td 49.259259 Tz (\(15.8 ) Tj 1.711111 0 Td 74.537037 Tz (mg ) Tj 1.263889 0 Td 55.092593 Tz (0.0824 ) Tj 2.177778 0 Td 64.166667 Tz (mmol\) ) Tj 2.061111 0 Td 60.493827 Tz (and ) Tj 1.244444 0 Td 50.925926 Tz (triethy ) Tj ET Q endstream endobj 294 0 obj << /Length 1 >> stream q endstream endobj 295 0 obj << /Length 40808 >> stream Q q 0.24 0 0 0.24 0 0 cm BT /F1 1 Tf 3 Tr 62.857143 0 0 62.857143 0 3023 Tm 17.325 0 Td 83.522727 Tz (US ) Tj 1.240909 0 Td 57.154882 Tz (8,497,371 ) Tj 3.388636 0 Td 74.242424 Tz (B2 ) Tj 52.857143 0 0 52.857143 0 2968 Tm 14.245946 0 Td 74.099099 Tz (19 ) Tj 51.428571 0 0 51.428571 0 2916.227895 Tm 6.338889 0 Td 47.800926 Tz (tion ) Tj 1.302778 0 Td 58.333333 Tz (on ) Tj 0.875 0 Td 42.12963 Tz (silica ) Tj 1.672222 0 Td 50.925926 Tz (yielded ) Tj 2.275 0 Td 64.409722 Tz (compound ) Tj 3.247222 0 Td 56.712963 Tz (26 ) Tj 0.855556 0 Td 45.37037 Tz (in ) Tj 0.680556 0 Td 53.796296 Tz (Table ) Tj 1.827778 0 Td 38.888889 Tz (1, ) Tj 0.622222 0 Td 57.037037 Tz (below ) Tj 1.925 0 Td 51.851852 Tz (\(35 ) Tj 1.108333 0 Td 59.41358 Tz (mg. ) Tj 58.571429 0 0 58.571429 0 2873 Tm 5.582927 0 Td 51.219512 Tz (75%\). ) Tj 1.843902 0 Td 54.065041 Tz ("H ) Tj 0.921951 0 Td 81.571816 Tz (NMR ) Tj 1.707317 0 Td 48.373984 Tz (\(300 ) Tj 1.4 0 Td 61.178862 Tz (MHz, ) Tj 1.72439 0 Td 54.539295 Tz (CDC1,\) ) Tj 2.219512 0 Td 45.528455 Tz (& ) Tj 0.546341 0 Td 45.528455 Tz (9.36-9.30 ) Tj 2.697561 0 Td 48.373984 Tz (\(m, ) Tj 1.195122 0 Td 44.105691 Tz (1H\), ) Tj 51.428571 0 0 51.428571 0 2834 Tm 6.377778 0 Td 51.131687 Tz (8.69-8.65 ) Tj 3.052778 0 Td 54.012346 Tz (\(m, ) Tj 1.322222 0 Td 51.041667 Tz (1H\), ) Tj 1.516667 0 Td 51.49177 Tz (7.89-7.82 ) Tj 3.091667 0 Td 50.771605 Tz (\(m. ) Tj 1.302778 0 Td 51.851852 Tz (1H\), ) Tj 1.536111 0 Td 51.131687 Tz (7.62-7.55 ) Tj 3.052778 0 Td 54.012346 Tz (\(m, ) Tj 1.302778 0 Td 51.851852 Tz (1H\), ) Tj 51.428571 0 0 51.428571 0 2795 Tm 6.358333 0 Td 51.49177 Tz (7.41-7.32 ) Tj 3.013889 0 Td 55.092593 Tz (\(m, ) Tj 1.283333 0 Td 51.041667 Tz (1H\), ) Tj 1.477778 0 Td 51.49177 Tz (7.00-6.92 ) Tj 3.033333 0 Td 51.851852 Tz (\(m. ) Tj 1.283333 0 Td 51.041667 Tz (1H\), ) Tj 1.438889 0 Td 50.771605 Tz (4.40-4.01 ) Tj 3.033333 0 Td 55.092593 Tz (\(m, ) Tj 1.283333 0 Td 53.148148 Tz (10H\), ) Tj 51.428571 0 0 51.428571 0 2756.844237 Tm 6.436111 0 Td 50.05144 Tz (1.53-1.44 ) Tj 2.916667 0 Td 51.851852 Tz (\(m, ) Tj 1.127778 0 Td 64.814815 Tz (3H\) ) Tj 1.341667 0 Td 59.953704 Tz (ppm. ) Tj 51.428571 0 0 51.428571 0 2684.295858 Tm 13.358333 0 Td 61.574074 Tz (Example ) Tj 2.761111 0 Td 58.333333 Tz (27 ) Tj 57.142857 0 0 57.142857 0 2606 Tm 7.0875 0 Td 50.261628 Tz (2-\(4-\(4-methylphenyl\)aminocarbonothioyl\)-1- ) Tj 51.428571 0 0 51.428571 0 2568 Tm 7.447222 0 Td 51.256614 Tz (piperazinyl\)-8-ethyl-5-oxo-5,8-dihydropyrido2,3-d ) Tj 51.428571 0 0 51.428571 0 2525.97137 Tm 10.15 0 Td 51.429147 Tz (pyrimidine-6-carboxylic ) Tj 7.291667 0 Td 50.231481 Tz (acid ) Tj 1.380556 0 Td 50.231481 Tz (\(27\) ) Tj 51.428571 0 0 51.428571 0 2444.183463 Tm 7.116667 0 Td 54.372428 Tz (Pipemidic ) Tj 3.111111 0 Td 51.851852 Tz (acid ) Tj 1.438889 0 Td 54.012346 Tz (\(89 ) Tj 1.205556 0 Td 60.493827 Tz (mg, ) Tj 1.302778 0 Td 53.796296 Tz (0.293 ) Tj 1.886111 0 Td 64.166667 Tz (mmol\) ) Tj 2.1 0 Td 60.493827 Tz (and ) Tj 1.263889 0 Td 46.759259 Tz (p-tolyl ) Tj 2.177778 0 Td 52.777778 Tz (isothio ) Tj 51.428571 0 0 51.428571 0 2403.613365 Tm 6.358333 0 Td 52.777778 Tz (cyanate ) Tj 2.333333 0 Td 54.012346 Tz (\(40 ) Tj 1.088889 0 Td 59.41358 Tz (mg, ) Tj 1.225 0 Td 54.444444 Tz (0.268 ) Tj 1.769444 0 Td 62.87037 Tz (mmol\) ) Tj 2.041667 0 Td 58.333333 Tz (were ) Tj 1.497222 0 Td 49.907407 Tz (used. ) Tj 1.672222 0 Td 46.720679 Tz (Purification ) Tj 3.480556 0 Td 58.333333 Tz (on ) Tj 0.816667 0 Td 43.209877 Tz (silica ) Tj 58.571429 0 0 58.571429 0 2365.832031 Tm 5.565854 0 Td 45.528455 Tz (yielded ) Tj 2.1 0 Td 56.554878 Tz (compound ) Tj 2.919512 0 Td 52.642276 Tz (27 ) Tj 0.853659 0 Td 41.260163 Tz (in ) Tj 0.665854 0 Td 47.804878 Tz (Table ) Tj 1.690244 0 Td 35.569106 Tz (1, ) Tj 0.631707 0 Td 50.650407 Tz (below ) Tj 1.792683 0 Td 46.476965 Tz (\(82 ) Tj 1.058537 0 Td 53.116531 Tz (mg, ) Tj 1.195122 0 Td 50.650407 Tz (68%\). ) Tj 1.77561 0 Td 55.487805 Tz ("H ) Tj 51.428571 0 0 51.428571 0 2323 Tm 6.358333 0 Td 92.901235 Tz (NMR ) Tj 1.808333 0 Td 55.092593 Tz (\(300 ) Tj 1.458333 0 Td 68.865741 Tz (MHz, ) Tj 1.827778 0 Td 73.888889 Tz (CDC1\) ) Tj 2.372222 0 Td 55.092593 Tz (& ) Tj 0.466667 0 Td 52.662037 Tz (9.32 ) Tj 1.419444 0 Td 38.888889 Tz (\(s, ) Tj 0.875 0 Td 52.662037 Tz (1H\), ) Tj 1.4 0 Td 53.472222 Tz (8.67 ) Tj 1.419444 0 Td 38.888889 Tz (\(s, ) Tj 0.913889 0 Td 51.041667 Tz (1H\), ) Tj 1.4 0 Td 51.851852 Tz (7.40 ) Tj 1.419444 0 Td 36.728395 Tz (\(s, ) Tj 51.428571 0 0 51.428571 0 2283.381418 Tm 6.416667 0 Td 51.851852 Tz (1H\), ) Tj 1.361111 0 Td 53.472222 Tz (7.17 ) Tj 1.419444 0 Td 52.211934 Tz (\(d.J=7.60 ) Tj 2.955556 0 Td 55.092593 Tz (Hz, ) Tj 1.166667 0 Td 53.472222 Tz (2H\), ) Tj 1.419444 0 Td 52.662037 Tz (7.09 ) Tj 1.361111 0 Td 39.969136 Tz (\(d. ) Tj 0.894444 0 Td 55.092593 Tz (J=7.44 ) Tj 2.1 0 Td 56.17284 Tz (Hz, ) Tj 1.127778 0 Td 54.282407 Tz (2H\), ) Tj 1.419444 0 Td 51.851852 Tz (4.33 ) Tj 1.4 0 Td 42.12963 Tz (\(q. ) Tj 51.428571 0 0 51.428571 0 2244 Tm 6.358333 0 Td 55.092593 Tz (J=6.40 ) Tj 2.294444 0 Td 55.092593 Tz (Hz, ) Tj 1.283333 0 Td 54.282407 Tz (2H\), ) Tj 1.594444 0 Td 50.05144 Tz (4.23-3.91 ) Tj 3.072222 0 Td 55.092593 Tz (\(m, ) Tj 1.283333 0 Td 54.282407 Tz (8H\), ) Tj 1.594444 0 Td 53.472222 Tz (2.34 ) Tj 1.555556 0 Td 37.808642 Tz (\(s, ) Tj 1.011111 0 Td 53.472222 Tz (3H\), ) Tj 1.652778 0 Td 51.041667 Tz (1.49 ) Tj 1.516667 0 Td 32.407407 Tz (\(t, ) Tj 51.428571 0 0 51.428571 0 2206.140845 Tm 6.358333 0 Td 53.472222 Tz (J7.03 ) Tj 2.197222 0 Td 54.012346 Tz (Hz, ) Tj 1.147222 0 Td 63.734568 Tz (3H\) ) Tj 1.302778 0 Td 61.574074 Tz (ppm. ) Tj 51.428571 0 0 51.428571 0 2133.295858 Tm 13.358333 0 Td 61.574074 Tz (Example ) Tj 2.761111 0 Td 58.333333 Tz (28 ) Tj 57.142857 0 0 57.142857 0 2055 Tm 7.175 0 Td 49.651163 Tz (2-\(4-\(4-chlorophenyl\)aminocarbonothioyl\)-1- ) Tj 51.428571 0 0 51.428571 0 2017 Tm 7.447222 0 Td 51.256614 Tz (piperazinyl\)-8-ethyl-5-oxo-5,8-dihydropyrido2,3-d ) Tj 51.428571 0 0 51.428571 0 1974.97137 Tm 10.15 0 Td 51.429147 Tz (pyrimidine-6-carboxylic ) Tj 7.291667 0 Td 50.231481 Tz (acid ) Tj 1.380556 0 Td 50.231481 Tz (\(28\) ) Tj 51.428571 0 0 51.428571 0 1894.451282 Tm 7.116667 0 Td 54.372428 Tz (Pipemidic ) Tj 3.111111 0 Td 51.851852 Tz (acid ) Tj 1.438889 0 Td 52.932099 Tz (\(58 ) Tj 1.205556 0 Td 59.41358 Tz (mg, ) Tj 1.283333 0 Td 51.851852 Tz (0.191 ) Tj 1.866667 0 Td 63.518519 Tz (mmol\) ) Tj 2.1 0 Td 59.41358 Tz (and ) Tj 1.263889 0 Td 52.777778 Tz (4-chlorophenyl ) Tj 51.428571 0 0 51.428571 0 1853.631068 Tm 6.358333 0 Td 50.231481 Tz (isothiocyanate ) Tj 4.375 0 Td 54.012346 Tz (\(27 ) Tj 1.205556 0 Td 58.333333 Tz (mg, ) Tj 1.263889 0 Td 53.796296 Tz (0.159 ) Tj 1.827778 0 Td 64.166667 Tz (mmol\) ) Tj 2.119444 0 Td 58.333333 Tz (were ) Tj 1.594444 0 Td 48.611111 Tz (used. ) Tj 1.730556 0 Td 46.990741 Tz (Purification ) Tj 51.428571 0 0 51.428571 0 1814.475936 Tm 6.358333 0 Td 61.574074 Tz (on ) Tj 1.011111 0 Td 42.12963 Tz (silica ) Tj 1.769444 0 Td 51.851852 Tz (yielded ) Tj 2.430556 0 Td 64.409722 Tz (compound ) Tj 3.383333 0 Td 55.092593 Tz (28 ) Tj 0.991667 0 Td 43.75 Tz (in ) Tj 0.777778 0 Td 54.444444 Tz (Table ) Tj 1.963889 0 Td 38.888889 Tz (1, ) Tj 0.758333 0 Td 57.037037 Tz (below ) Tj 2.041667 0 Td 54.012346 Tz (\(50 ) Tj 1.263889 0 Td 58.333333 Tz (mg. ) Tj 58.571429 0 0 58.571429 0 1772 Tm 5.6 0 Td 50.650407 Tz (67%\). ) Tj 1.77561 0 Td 54.065041 Tz ("H ) Tj 0.836585 0 Td 81.571816 Tz (NMR ) Tj 1.656098 0 Td 47.662602 Tz (\(300 ) Tj 1.34878 0 Td 60.46748 Tz (MHz, ) Tj 1.690244 0 Td 63.739837 Tz (CDC1\) ) Tj 2.15122 0 Td 42.682927 Tz (& ) Tj 0.495122 0 Td 44.817073 Tz (9.34 ) Tj 1.280488 0 Td 34.146341 Tz (\(s, ) Tj 0.870732 0 Td 44.817073 Tz (1H\), ) Tj 1.280488 0 Td 46.239837 Tz (8.68 ) Tj 1.314634 0 Td 33.197832 Tz (\(s, ) Tj 51.428571 0 0 51.428571 0 1732 Tm 6.416667 0 Td 51.851852 Tz (1H\), ) Tj 1.458333 0 Td 51.851852 Tz (7.36-7.34 ) Tj 3.013889 0 Td 54.012346 Tz (\(m, ) Tj 1.225 0 Td 53.472222 Tz (2H\), ) Tj 1.516667 0 Td 52.662037 Tz (7.17 ) Tj 1.477778 0 Td 39.969136 Tz (\(d. ) Tj 0.972222 0 Td 54.552469 Tz (J=8.70 ) Tj 2.197222 0 Td 55.092593 Tz (Hz, ) Tj 1.225 0 Td 55.092593 Tz (2H\), ) Tj 1.536111 0 Td 51.131687 Tz (4.39-4.28 ) Tj 51.428571 0 0 51.428571 0 1693.794702 Tm 6.377778 0 Td 52.932099 Tz (\(m. ) Tj 1.127778 0 Td 55.902778 Tz (2H\), ) Tj 1.516667 0 Td 51.131687 Tz (4.28-3.93 ) Tj 2.994444 0 Td 52.932099 Tz (\(m, ) Tj 1.147222 0 Td 54.282407 Tz (8H\), ) Tj 1.555556 0 Td 51.041667 Tz (1.49 ) Tj 1.4 0 Td 34.567901 Tz (\(t, ) Tj 0.816667 0 Td 54.552469 Tz (J=6.68 ) Tj 2.197222 0 Td 52.932099 Tz (Hz, ) Tj 1.147222 0 Td 63.734568 Tz (3H\) ) Tj 1.322222 0 Td 60.763889 Tz (ppm. ) Tj 52.857143 0 0 52.857143 0 1621.269006 Tm 12.978378 0 Td 60.36036 Tz (Example ) Tj 2.686486 0 Td 58.333333 Tz (29 ) Tj 57.142857 0 0 57.142857 0 1539 Tm 6.65 0 Td 51.333333 Tz (2-\(4-\(3-iodophenyl\)aminocarbonothioyl-1-piper ) Tj 51.428571 0 0 51.428571 0 1498 Tm 7.486111 0 Td 51.719577 Tz (azinyl\)-8-ethyl-5-oxo-5,8-dihydropyrido2,3-dipyri ) Tj 51.428571 0 0 51.428571 0 1454.682243 Tm 10.733333 0 Td 51.851852 Tz (midine-6-carboxylic ) Tj 6.105556 0 Td 51.041667 Tz (acid ) Tj 1.419444 0 Td 49.421296 Tz (\(29\) ) Tj 51.428571 0 0 51.428571 0 1370.290621 Tm 7.116667 0 Td 54.372428 Tz (Pipemidic ) Tj 3.208333 0 Td 51.041667 Tz (acid ) Tj 1.497222 0 Td 55.092593 Tz (\(40 ) Tj 1.263889 0 Td 60.493827 Tz (mg, ) Tj 1.380556 0 Td 53.796296 Tz (0.133 ) Tj 1.944444 0 Td 64.166667 Tz (mmol\) ) Tj 2.197222 0 Td 59.41358 Tz (and ) Tj 1.341667 0 Td 53.742284 Tz (3-iodophenyl ) Tj 51.428571 0 0 51.428571 0 1326.643902 Tm 6.358333 0 Td 50.231481 Tz (isothiocyanate ) Tj 4.375 0 Td 52.932099 Tz (\(29 ) Tj 1.205556 0 Td 58.333333 Tz (mg, ) Tj 1.263889 0 Td 51.851852 Tz (0.111 ) Tj 1.827778 0 Td 64.166667 Tz (mmol\) ) Tj 2.119444 0 Td 58.333333 Tz (were ) Tj 1.594444 0 Td 48.611111 Tz (used. ) Tj 1.730556 0 Td 46.990741 Tz (Purification ) Tj 51.428571 0 0 51.428571 0 1285.485255 Tm 6.358333 0 Td 61.574074 Tz (on ) Tj 1.011111 0 Td 42.12963 Tz (silica ) Tj 1.769444 0 Td 51.851852 Tz (yielded ) Tj 2.430556 0 Td 64.409722 Tz (compound ) Tj 3.383333 0 Td 55.092593 Tz (29 ) Tj 0.991667 0 Td 43.75 Tz (in ) Tj 0.777778 0 Td 54.444444 Tz (Table ) Tj 1.963889 0 Td 38.888889 Tz (1, ) Tj 0.758333 0 Td 57.037037 Tz (below ) Tj 2.041667 0 Td 51.851852 Tz (\(57 ) Tj 1.263889 0 Td 58.333333 Tz (mg, ) Tj 57.142857 0 0 57.142857 0 1241 Tm 5.74 0 Td 51.916667 Tz (90%\). ) Tj 1.82 0 Td 55.416667 Tz ("H ) Tj 0.8575 0 Td 83.611111 Tz (NMR ) Tj 1.6975 0 Td 48.854167 Tz (\(250 ) Tj 1.3825 0 Td 61.979167 Tz (MHz, ) Tj 1.7325 0 Td 65.333333 Tz (CDC1\) ) Tj 2.205 0 Td 43.75 Tz (& ) Tj 0.5075 0 Td 45.208333 Tz (9.33 ) Tj 1.3125 0 Td 35 Tz (\(s, ) Tj 0.8925 0 Td 45.9375 Tz (1H\), ) Tj 1.3125 0 Td 46.666667 Tz (8.73 ) Tj 1.3475 0 Td 34.027778 Tz (\(s, ) Tj 51.428571 0 0 51.428571 0 1199 Tm 6.416667 0 Td 51.041667 Tz (1H\), ) Tj 1.555556 0 Td 51.131687 Tz (7.66-7.64 ) Tj 3.052778 0 Td 51.851852 Tz (\(m. ) Tj 1.302778 0 Td 51.851852 Tz (1H\), ) Tj 1.536111 0 Td 50.05144 Tz (7.54-7.51 ) Tj 3.072222 0 Td 52.932099 Tz (\(m. ) Tj 1.322222 0 Td 51.041667 Tz (1H\), ) Tj 1.516667 0 Td 51.49177 Tz (7.40-7.24 ) Tj 3.052778 0 Td 54.012346 Tz (\(m, ) Tj 51.428571 0 0 51.428571 0 1158 Tm 6.416667 0 Td 51.041667 Tz (1H\), ) Tj 1.555556 0 Td 51.131687 Tz (7.12-7.06 ) Tj 3.052778 0 Td 51.851852 Tz (\(m. ) Tj 1.302778 0 Td 51.851852 Tz (1H\), ) Tj 1.516667 0 Td 50.411523 Tz (4.48-4.31 ) Tj 3.091667 0 Td 52.932099 Tz (\(m, ) Tj 1.225 0 Td 55.092593 Tz (2H\), ) Tj 1.613889 0 Td 50.771605 Tz (4.27-3.93 ) Tj 3.052778 0 Td 54.012346 Tz (\(m, ) Tj 51.428571 0 0 51.428571 0 1117.533679 Tm 6.377778 0 Td 53.472222 Tz (8H\), ) Tj 1.555556 0 Td 50.05144 Tz (1.34-1.17 ) Tj 2.916667 0 Td 51.851852 Tz (\(m, ) Tj 1.147222 0 Td 63.734568 Tz (3H\) ) Tj 1.322222 0 Td 59.953704 Tz (ppm. ) Tj 51.428571 0 0 51.428571 0 1043.232558 Tm 13.338889 0 Td 62.037037 Tz (Example ) Tj 2.761111 0 Td 61.574074 Tz (30 ) Tj 57.142857 0 0 57.142857 0 961 Tm 7.2275 0 Td 49.244186 Tz (2-\(4-\(2-fluorophenyl\)aminocarbonothioyl\)-1- ) Tj 51.428571 0 0 51.428571 0 920 Tm 7.447222 0 Td 51.256614 Tz (piperazinyl\)-8-ethyl-5-oxo-5,8-dihydropyrido2,3-d ) Tj 51.428571 0 0 51.428571 0 876.97137 Tm 10.15 0 Td 51.429147 Tz (pyrimidine-6-carboxylic ) Tj 7.291667 0 Td 50.231481 Tz (acid ) Tj 1.380556 0 Td 50.231481 Tz (\(30\) ) Tj 51.428571 0 0 51.428571 0 792.263959 Tm 7.116667 0 Td 54.372428 Tz (Pipemidic ) Tj 3.072222 0 Td 51.851852 Tz (acid ) Tj 1.419444 0 Td 51.851852 Tz (\(25 ) Tj 1.147222 0 Td 77.777778 Tz (mg ) Tj 1.263889 0 Td 55.092593 Tz (0.0824 ) Tj 2.177778 0 Td 64.166667 Tz (mmol\) ) Tj 2.080556 0 Td 59.41358 Tz (and ) Tj 1.244444 0 Td 51.157407 Tz (2-fluorophenyl ) Tj 51.428571 0 0 51.428571 0 748.06913 Tm 6.358333 0 Td 50.231481 Tz (isothiocyanate ) Tj 4.355556 0 Td 55.092593 Tz (\(10 ) Tj 1.147222 0 Td 52.932099 Tz (uL, ) Tj 1.108333 0 Td 55.092593 Tz (0.0824 ) Tj 2.177778 0 Td 62.87037 Tz (mmol\) ) Tj 2.061111 0 Td 59.143519 Tz (were ) Tj 1.575 0 Td 49.259259 Tz (used. ) Tj 1.691667 0 Td 46.990741 Tz (Purification ) Tj 51.428571 0 0 51.428571 0 708.466667 Tm 6.358333 0 Td 61.574074 Tz (on ) Tj 1.011111 0 Td 42.12963 Tz (silica ) Tj 1.769444 0 Td 51.851852 Tz (yielded ) Tj 2.430556 0 Td 64.409722 Tz (compound ) Tj 3.363889 0 Td 61.574074 Tz (30 ) Tj 1.011111 0 Td 43.75 Tz (in ) Tj 0.777778 0 Td 54.444444 Tz (Table ) Tj 1.963889 0 Td 38.888889 Tz (1, ) Tj 0.758333 0 Td 57.037037 Tz (below ) Tj 2.041667 0 Td 51.851852 Tz (\(24 ) Tj 1.263889 0 Td 58.333333 Tz (mg. ) Tj 58.571429 0 0 58.571429 0 663 Tm 5.6 0 Td 50.650407 Tz (64%\). ) Tj 1.77561 0 Td 54.065041 Tz ("H ) Tj 0.836585 0 Td 81.571816 Tz (NMR ) Tj 1.656098 0 Td 47.662602 Tz (\(300 ) Tj 1.34878 0 Td 60.46748 Tz (MHz, ) Tj 1.690244 0 Td 63.739837 Tz (CDC1\) ) Tj 2.15122 0 Td 42.682927 Tz (& ) Tj 0.495122 0 Td 44.817073 Tz (9.35 ) Tj 1.280488 0 Td 34.146341 Tz (\(s, ) Tj 0.870732 0 Td 44.817073 Tz (1H\), ) Tj 1.280488 0 Td 46.239837 Tz (8.69 ) Tj 1.314634 0 Td 33.197832 Tz (\(s. ) Tj 51.428571 0 0 51.428571 0 621.423338 Tm 6.416667 0 Td 51.041667 Tz (1H\), ) Tj 1.555556 0 Td 52.662037 Tz (7.64 ) Tj 1.536111 0 Td 34.567901 Tz (\(t, ) Tj 0.894444 0 Td 55.092593 Tz (J=7.34 ) Tj 2.294444 0 Td 54.012346 Tz (Hz, ) Tj 1.341667 0 Td 51.041667 Tz (1H\), ) Tj 1.536111 0 Td 51.131687 Tz (7.21-7.12 ) Tj 3.052778 0 Td 54.012346 Tz (\(m, ) Tj 1.263889 0 Td 53.472222 Tz (3H\), ) Tj 1.594444 0 Td 52.662037 Tz (4.35 ) Tj 1.555556 0 Td 42.12963 Tz (\(q, ) Tj 51.428571 0 0 51.428571 0 580 Tm 6.358333 0 Td 55.092593 Tz (J=6.90 ) Tj 2.197222 0 Td 55.092593 Tz (Hz, ) Tj 1.225 0 Td 53.472222 Tz (2H\), ) Tj 1.497222 0 Td 66.203704 Tz (428-402 ) Tj 3.013889 0 Td 52.932099 Tz (\(m, ) Tj 1.166667 0 Td 54.282407 Tz (8H\), ) Tj 1.575 0 Td 51.041667 Tz (1.50 ) Tj 1.438889 0 Td 33.487654 Tz (\(t, ) Tj 0.816667 0 Td 54.012346 Tz (J=7.09 ) Tj 2.197222 0 Td 55.092593 Tz (Hz, ) Tj 1.205556 0 Td 62.654321 Tz (3H\) ) Tj 38.571429 0 0 38.571429 0 544 Tm 8.451852 0 Td 82.098765 Tz (ppm. ) Tj 51.428571 0 0 51.428571 0 465.409639 Tm 13.358333 0 Td 61.574074 Tz (Example ) Tj 2.761111 0 Td 53.472222 Tz (31 ) Tj 57.142857 0 0 57.142857 0 383 Tm 7.21 0 Td 50.555556 Tz (2-\(4-\(4-trifluoromethylphenyl\)aminocarbono ) Tj 57.142857 0 0 57.142857 0 342 Tm 6.7025 0 Td 46.72619 Tz (thioyl-1-piperazinyl\)-8-ethyl-5-oxo-5,8-dihydropy ) Tj 51.428571 0 0 51.428571 0 299.478528 Tm 8.555556 0 Td 51.851852 Tz (rido2,3-dipyrimidine-6-carboxylic ) Tj 10.461111 0 Td 51.041667 Tz (acid ) Tj 1.419444 0 Td 49.421296 Tz (\(31\) ) Tj 51.428571 0 0 51.428571 0 212.145833 Tm 7.116667 0 Td 54.372428 Tz (Pipemidic ) Tj 3.169444 0 Td 50.231481 Tz (acid ) Tj 1.477778 0 Td 52.932099 Tz (\(30 ) Tj 1.225 0 Td 59.41358 Tz (mg, ) Tj 1.322222 0 Td 55.092593 Tz (0.0989 ) Tj 2.255556 0 Td 64.166667 Tz (mmol\) ) Tj 2.158333 0 Td 59.41358 Tz (and ) Tj 1.302778 0 Td 52.662037 Tz (4-trifluorom ) Tj 51.428571 0 0 51.428571 0 172.456853 Tm 6.358333 0 Td 51.557239 Tz (ethylphenyl ) Tj 3.733333 0 Td 50 Tz (isothiocyanate ) Tj 4.530556 0 Td 49.907407 Tz (\(16.7 ) Tj 1.827778 0 Td 77.777778 Tz (mg ) Tj 1.4 0 Td 55.092593 Tz (0.0824 ) Tj 2.352778 0 Td 62.87037 Tz (mmol\) ) Tj 2.216667 0 Td 59.143519 Tz (were ) Tj 30 0 0 30 0 2547 Tm 41.666667 0 Td 75 Tz (10 ) Tj 30 0 0 30 0 2339 Tm 41.666667 0 Td 72.222222 Tz (15 ) Tj 30 0 0 30 0 1923 Tm 41.6 0 Td 77.777778 Tz (25 ) Tj 30 0 0 30 0 1716 Tm 41.6 0 Td 80.555556 Tz (30 ) Tj 30 0 0 30 0 1507 Tm 41.6 0 Td 77.777778 Tz (35 ) Tj 30 0 0 30 0 1299 Tm 41.566667 0 Td 83.333333 Tz (40 ) Tj 30 0 0 30 0 1091 Tm 41.566667 0 Td 80.555556 Tz (45 ) Tj 30 0 0 30 0 883 Tm 41.6 0 Td 80.555556 Tz (50 ) Tj 30 0 0 30 0 675 Tm 41.6 0 Td 77.777778 Tz (55 ) Tj 30 0 0 30 0 467 Tm 41.633333 0 Td 77.777778 Tz (60 ) Tj 30 0 0 30 0 259 Tm 41.633333 0 Td 75 Tz (65 ) Tj 52.857143 0 0 52.857143 0 2968 Tm 32.635135 0 Td 77.252252 Tz (20 ) Tj 51.428571 0 0 51.428571 0 2915.69 Tm 25.277778 0 Td 49.907407 Tz (used. ) Tj 1.730556 0 Td 46.720679 Tz (Purification ) Tj 3.558333 0 Td 59.953704 Tz (on ) Tj 0.933333 0 Td 42.12963 Tz (silica ) Tj 1.711111 0 Td 50.462963 Tz (yielded ) Tj 2.294444 0 Td 64.814815 Tz (compound ) Tj 3.286111 0 Td 53.472222 Tz (31 ) Tj 0.933333 0 Td 42.12963 Tz (in ) Tj 0.680556 0 Td 54.444444 Tz (Table ) Tj 1.886111 0 Td 37.268519 Tz (1, ) Tj 58.571429 0 0 58.571429 0 2869.637887 Tm 22.195122 0 Td 51.219512 Tz (below ) Tj 1.72439 0 Td 42.682927 Tz (\(31 ) Tj 0.990244 0 Td 52.168022 Tz (mg, ) Tj 1.109756 0 Td 51.219512 Tz (77%\). ) Tj 1.929268 0 Td 79.674797 Tz (H ) Tj 0.614634 0 Td 81.571816 Tz (NMR ) Tj 1.621951 0 Td 48.373984 Tz (\(300 ) Tj 1.297561 0 Td 60.46748 Tz (MHz, ) Tj 1.639024 0 Td 54.065041 Tz (CDC1,\) ) Tj 2.117073 0 Td 45.528455 Tz (& ) Tj 0.426829 0 Td 46.239837 Tz (9.34 ) Tj 1.280488 0 Td 32.249322 Tz (\(s, ) Tj 51.428571 0 0 51.428571 0 2826 Tm 25.355556 0 Td 51.851852 Tz (1H\), ) Tj 1.4 0 Td 53.472222 Tz (8.69 ) Tj 1.477778 0 Td 37.808642 Tz (\(s, ) Tj 0.913889 0 Td 51.041667 Tz (1H\), ) Tj 1.438889 0 Td 51.49177 Tz (7.65-7.57 ) Tj 2.955556 0 Td 54.012346 Tz (\(m, ) Tj 1.166667 0 Td 53.472222 Tz (2H\), ) Tj 1.458333 0 Td 49.421296 Tz (7.51 ) Tj 1.458333 0 Td 36.728395 Tz (\(s, ) Tj 0.894444 0 Td 53.472222 Tz (1H\), ) Tj 1.477778 0 Td 49.691358 Tz (7.37-7.31 ) Tj 51.428571 0 0 51.428571 0 2782.404551 Tm 25.316667 0 Td 52.932099 Tz (\(m. ) Tj 1.127778 0 Td 54.282407 Tz (2H\), ) Tj 1.477778 0 Td 53.472222 Tz (4.34 ) Tj 1.438889 0 Td 43.209877 Tz (\(q, ) Tj 0.933333 0 Td 54.552469 Tz (J=6.80 ) Tj 2.197222 0 Td 54.012346 Tz (Hz, ) Tj 1.147222 0 Td 53.472222 Tz (2H\), ) Tj 1.458333 0 Td 52.211934 Tz (4.27-3.97 ) Tj 2.994444 0 Td 51.851852 Tz (\(m, ) Tj 1.127778 0 Td 54.282407 Tz (8H\), ) Tj 1.555556 0 Td 50.231481 Tz (1.49 ) Tj 1.380556 0 Td 32.407407 Tz (\(t, ) Tj 51.428571 0 0 51.428571 0 2740.666667 Tm 25.297222 0 Td 50.462963 Tz (J=7.25, ) Tj 2.333333 0 Td 52.662037 Tz (7.25 ) Tj 1.477778 0 Td 55.092593 Tz (Hz, ) Tj 1.166667 0 Td 64.814815 Tz (3H\) ) Tj 1.322222 0 Td 60.763889 Tz (ppm. ) Tj 48.571429 0 0 48.571429 0 2697 Tm 27.547059 0 Td 70.343137 Tz (As ) Tj 1.008824 0 Td 56.27451 Tz (noted ) Tj 1.791176 0 Td 56.045752 Tz (above, ) Tj 2.161765 0 Td 45.465686 Tz (this ) Tj 1.235294 0 Td 52.614379 Tz (invention ) Tj 2.985294 0 Td 41.176471 Tz (is ) Tj 0.658824 0 Td 51.470588 Tz (directed ) Tj 2.552941 0 Td 51.470588 Tz (to ) Tj 0.720588 0 Td 61.764706 Tz (a ) Tj 0.535294 0 Td 54.215686 Tz (novel ) Tj 1.791176 0 Td 64.052288 Tz (method ) Tj 51.428571 0 0 51.428571 0 2656.28 Tm 25.297222 0 Td 56.712963 Tz (of ) Tj 0.738889 0 Td 46.990741 Tz (treating ) Tj 2.372222 0 Td 47.800926 Tz (patients ) Tj 2.469444 0 Td 51.851852 Tz (with ) Tj 1.419444 0 Td 47.395833 Tz (Suitable ) Tj 2.372222 0 Td 78.858025 Tz (ATX ) Tj 1.575 0 Td 47.638889 Tz (inhibiting ) Tj 2.994444 0 Td 58.333333 Tz (compounds. ) Tj 51.428571 0 0 51.428571 0 2611.496887 Tm 25.316667 0 Td 59.143519 Tz (Such ) Tj 1.672222 0 Td 62.294239 Tz (compounds ) Tj 3.636111 0 Td 58.333333 Tz (were ) Tj 1.633333 0 Td 54.444444 Tz (determined ) Tj 3.538889 0 Td 53.240741 Tz (through ) Tj 2.488889 0 Td 55.092593 Tz (a ) Tj 0.602778 0 Td 51.041667 Tz (very ) Tj 1.516667 0 Td 43.930041 Tz (efficient ) Tj 51.428571 0 0 51.428571 0 2568.698885 Tm 25.316667 0 Td 51.49177 Tz (screening ) Tj 2.994444 0 Td 51.527778 Tz (procedure, ) Tj 3.325 0 Td 58.333333 Tz (and ) Tj 1.244444 0 Td 46.666667 Tz (exist ) Tj 1.594444 0 Td 51.851852 Tz (as ) Tj 0.875 0 Td 50.231481 Tz (lead ) Tj 1.419444 0 Td 61.934156 Tz (compounds ) Tj 3.597222 0 Td 52.662037 Tz (with ) Tj 1.477778 0 Td 51.851852 Tz (the ) Tj 51.428571 0 0 51.428571 0 2524.876847 Tm 25.297222 0 Td 47.170782 Tz (potential ) Tj 2.761111 0 Td 46.990741 Tz (to ) Tj 0.797222 0 Td 44.074074 Tz (treat ) Tj 1.575 0 Td 47.727273 Tz (metastasis, ) Tj 3.383333 0 Td 46.585648 Tz (obesity, ) Tj 2.508333 0 Td 51.262626 Tz (neuropathic ) Tj 3.616667 0 Td 48.611111 Tz (pain, ) Tj 1.691667 0 Td 62.654321 Tz (ath ) Tj 48.571429 0 0 48.571429 0 2479 Tm 26.785294 0 Td 50.326797 Tz (erosclerosis ) Tj 3.788235 0 Td 62.908497 Tz (and ) Tj 1.317647 0 Td 58.333333 Tz (rheumatoid ) Tj 3.644118 0 Td 43.578431 Tz (arthritis, ) Tj 2.779412 0 Td 46.323529 Tz (at ) Tj 0.761765 0 Td 43.464052 Tz (least, ) Tj 1.75 0 Td 53.75817 Tz (within ) Tj 2.141176 0 Td 54.901961 Tz (a ) Tj 0.555882 0 Td 97.222222 Tz (mam ) Tj 51.428571 0 0 51.428571 0 2433.86747 Tm 25.297222 0 Td 55.092593 Tz (malian ) Tj 2.391667 0 Td 52.5 Tz (body. ) Tj 1.983333 0 Td 66.435185 Tz (As ) Tj 1.225 0 Td 51.851852 Tz (described ) Tj 3.188889 0 Td 52.932099 Tz (above, ) Tj 2.352778 0 Td 48.611111 Tz (the ) Tj 1.283333 0 Td 50.05144 Tz (autotaxin ) Tj 3.15 0 Td 62.87037 Tz (\(ATX\) ) Tj 51.428571 0 0 51.428571 0 2392.764706 Tm 25.297222 0 Td 63.194444 Tz (enzyme ) Tj 2.391667 0 Td 56.30787 Tz (promotes ) Tj 2.838889 0 Td 43.75 Tz (cell ) Tj 1.205556 0 Td 51.851852 Tz (migration ) Tj 2.916667 0 Td 60.493827 Tz (and ) Tj 1.225 0 Td 47.530864 Tz (invasion, ) Tj 2.702778 0 Td 50.231481 Tz (thus ) Tj 1.361111 0 Td 47.314815 Tz (inhibition ) Tj 51.428571 0 0 51.428571 0 2347.545565 Tm 25.297222 0 Td 56.712963 Tz (of ) Tj 0.758333 0 Td 77.777778 Tz (ATX ) Tj 1.555556 0 Td 40.509259 Tz (is ) Tj 0.641667 0 Td 59.953704 Tz (of ) Tj 0.797222 0 Td 52.5 Tz (value ) Tj 1.730556 0 Td 48.611111 Tz (for ) Tj 0.991667 0 Td 51.527778 Tz (prevention ) Tj 3.266667 0 Td 58.333333 Tz (of ) Tj 0.777778 0 Td 49.907407 Tz (metastasis ) Tj 3.169444 0 Td 58.333333 Tz (and ) Tj 1.244444 0 Td 48.611111 Tz (the ) Tj 1.011111 0 Td 51.851852 Tz (other ) Tj 51.428571 0 0 51.428571 0 2305.728248 Tm 25.297222 0 Td 53.472222 Tz (maladies ) Tj 2.761111 0 Td 53.148148 Tz (noted ) Tj 1.75 0 Td 48.021886 Tz (previously. ) Tj 3.383333 0 Td 45.37037 Tz (In ) Tj 0.7 0 Td 47.890947 Tz (addition, ) Tj 2.741667 0 Td 51.311728 Tz (assays ) Tj 2.022222 0 Td 59.143519 Tz (were ) Tj 1.536111 0 Td 53.877315 Tz (prepared ) Tj 51.428571 0 0 51.428571 0 2261.034158 Tm 25.297222 0 Td 49.691358 Tz (for ) Tj 0.991667 0 Td 53.914141 Tz (comparative ) Tj 3.713889 0 Td 45.046296 Tz (reactivity ) Tj 2.858333 0 Td 57.523148 Tz (measurements ) Tj 4.277778 0 Td 53.472222 Tz (with ) Tj 1.419444 0 Td 51.203704 Tz (other ) Tj 1.672222 0 Td 73.45679 Tz (NPP ) Tj 1.458333 0 Td 59.41358 Tz (iso ) Tj 51.428571 0 0 51.428571 0 2216.708831 Tm 25.297222 0 Td 56.388889 Tz (forms ) Tj 1.827778 0 Td 64.814815 Tz (\(NPP6 ) Tj 2.061111 0 Td 58.333333 Tz (and ) Tj 1.147222 0 Td 65.462963 Tz (NPP7\) ) Tj 2.1 0 Td 68.865741 Tz (\(ATX ) Tj 1.788889 0 Td 37.268519 Tz (is ) Tj 0.583333 0 Td 62.222222 Tz (NPP2, ) Tj 2.002778 0 Td 50.231481 Tz (as ) Tj 0.758333 0 Td 53.148148 Tz (noted ) Tj 1.691667 0 Td 48.341049 Tz (previously\). ) Tj 40 0 0 40 0 2179 Tm 32.55 0 Td 76.041667 Tz (Such ) Tj 2.1 0 Td 74.404762 Tz (methods ) Tj 3.4 0 Td 75 Tz (were ) Tj 2 0 Td 71.759259 Tz (conducted ) Tj 4.1 0 Td 64.583333 Tz (as ) Tj 1.025 0 Td 61.979167 Tz (follows: ) Tj 51.428571 0 0 51.428571 0 2129.355987 Tm 25.297222 0 Td 78.858025 Tz (ATX ) Tj 1.633333 0 Td 46.990741 Tz (Inhibition ) Tj 2.994444 0 Td 58.981481 Tz (Assay ) Tj 51.428571 0 0 51.428571 0 2085.99005 Tm 26.016667 0 Td 78.858025 Tz (ATX ) Tj 1.575 0 Td 46.666667 Tz (inhibition ) Tj 2.936111 0 Td 60.493827 Tz (was ) Tj 1.244444 0 Td 54.166667 Tz (assayed ) Tj 2.391667 0 Td 53.796296 Tz (using ) Tj 1.730556 0 Td 48.611111 Tz (the ) Tj 0.991667 0 Td 48.251029 Tz (substrate ) Tj 2.761111 0 Td 55.902778 Tz (FS-3 ) Tj 1.497222 0 Td 67.24537 Tz (\(Ech ) Tj 51.428571 0 0 51.428571 0 2040.701583 Tm 25.297222 0 Td 51.851852 Tz (elon ) Tj 1.458333 0 Td 49.691358 Tz (Biosciences, ) Tj 3.752778 0 Td 42.12963 Tz (Inc., ) Tj 1.419444 0 Td 47.800926 Tz (Salt ) Tj 1.322222 0 Td 58.333333 Tz (Lake ) Tj 1.516667 0 Td 46.666667 Tz (City, ) Tj 1.555556 0 Td 53.148148 Tz (Utah, ) Tj 1.75 0 Td 61.574074 Tz (USA\). ) Tj 2.002778 0 Td 62.654321 Tz (The ) Tj 1.283333 0 Td 56.712963 Tz (FS-3 ) Tj 51.428571 0 0 51.428571 0 1996.787208 Tm 25.297222 0 Td 51.851852 Tz (assay ) Tj 1.827778 0 Td 55.902778 Tz (used ) Tj 1.652778 0 Td 59.41358 Tz (~10 ) Tj 1.322222 0 Td 52.5 Tz (times ) Tj 1.866667 0 Td 51.311728 Tz (concentrated ) Tj 3.966667 0 Td 51.557239 Tz (conditioned ) Tj 3.675 0 Td 52.824074 Tz (serum-free ) Tj 51.428571 0 0 51.428571 0 1953 Tm 25.297222 0 Td 65.354938 Tz (medium ) Tj 2.625 0 Td 69.351852 Tz (\(CCM\) ) Tj 2.333333 0 Td 57.523148 Tz (from ) Tj 1.633333 0 Td 72.916667 Tz (MDA-MB-435 ) Tj 4.608333 0 Td 44.074074 Tz (cells ) Tj 1.555556 0 Td 48.611111 Tz (as ) Tj 0.855556 0 Td 49.691358 Tz (the ) Tj 1.127778 0 Td 51.851852 Tz (source ) Tj 2.119444 0 Td 58.333333 Tz (of ) Tj 51.428571 0 0 51.428571 0 1910.552534 Tm 25.297222 0 Td 66.435185 Tz (ATX, ) Tj 1.827778 0 Td 53.796296 Tz (while ) Tj 1.827778 0 Td 89.660494 Tz (CCM ) Tj 1.827778 0 Td 56.532922 Tz (comprised ) Tj 3.266667 0 Td 49.691358 Tz (one-third ) Tj 2.877778 0 Td 61.574074 Tz (of ) Tj 0.875 0 Td 47.530864 Tz (the ) Tj 1.108333 0 Td 42.12963 Tz (total ) Tj 1.516667 0 Td 55.092593 Tz (volume. ) Tj 51.428571 0 0 51.428571 0 1867.556382 Tm 25.297222 0 Td 63.734568 Tz (The ) Tj 1.341667 0 Td 41.481481 Tz (final ) Tj 1.477778 0 Td 59.953704 Tz (volume ) Tj 2.333333 0 Td 48.611111 Tz (for ) Tj 1.069444 0 Td 55.902778 Tz (FS-3 ) Tj 1.575 0 Td 60.493827 Tz (was ) Tj 1.283333 0 Td 56.532922 Tz (comprised ) Tj 3.208333 0 Td 59.953704 Tz (of ) Tj 0.797222 0 Td 50.771605 Tz (the ) Tj 1.088889 0 Td 47.890947 Tz (substrate ) Tj 2.741667 0 Td 46.990741 Tz (at ) Tj 51.428571 0 0 51.428571 0 1826.403487 Tm 25.297222 0 Td 53.240741 Tz (varying ) Tj 2.508333 0 Td 50.462963 Tz (concentrations ) Tj 4.530556 0 Td 60.493827 Tz (and ) Tj 1.380556 0 Td 61.574074 Tz (30 ) Tj 1.088889 0 Td 79.398148 Tz (uM ) Tj 1.283333 0 Td 49.373638 Tz (charcoal-stripped ) Tj 5.347222 0 Td 44.074074 Tz (fatty ) Tj 51.428571 0 0 51.428571 0 1779.926115 Tm 25.297222 0 Td 51.041667 Tz (acid ) Tj 1.438889 0 Td 46.990741 Tz (free ) Tj 1.361111 0 Td 76.697531 Tz (BSA ) Tj 1.594444 0 Td 58.333333 Tz (\(Sigma ) Tj 2.294444 0 Td 51.446759 Tz (Aldrich\) ) Tj 2.683333 0 Td 45.37037 Tz (in ) Tj 0.738889 0 Td 52.5 Tz (assay ) Tj 1.808333 0 Td 49.151235 Tz (buffer ) Tj 1.963889 0 Td 45.37037 Tz (\(1 ) Tj 0.855556 0 Td 97.222222 Tz (mM ) Tj 1.380556 0 Td 56.712963 Tz (each ) Tj 52.857143 0 0 52.857143 0 1735.560248 Tm 24.613514 0 Td 63.851351 Tz (CaCl ) Tj 1.854054 0 Td 56.756757 Tz (and ) Tj 1.135135 0 Td 69.369369 Tz (MgCl, ) Tj 2.251351 0 Td 50.45045 Tz (5 ) Tj 0.472973 0 Td 96.171171 Tz (mM ) Tj 1.305405 0 Td 55.968468 Tz (KC1, ) Tj 1.532432 0 Td 55.705706 Tz (140 ) Tj 1.116216 0 Td 70.720721 Tz (mMNaCl, ) Tj 3.121622 0 Td 56.756757 Tz (50 ) Tj 0.832432 0 Td 96.171171 Tz (mM ) Tj 1.267568 0 Td 45.720721 Tz (Tris ) Tj 1.210811 0 Td 74.099099 Tz (pH ) Tj 51.428571 0 0 51.428571 0 1691 Tm 25.316667 0 Td 42.777778 Tz (8.0\). ) Tj 52.857143 0 0 52.857143 0 1649.42 Tm 25.294595 0 Td 51.501502 Tz (All ) Tj 1.059459 0 Td 50.45045 Tz (assays ) Tj 1.948649 0 Td 56.756757 Tz (were ) Tj 1.494595 0 Td 55.355355 Tz (performed ) Tj 3.121622 0 Td 45.720721 Tz (in ) Tj 0.643243 0 Td 51.801802 Tz (96-well ) Tj 2.327027 0 Td 46.246246 Tz (plates ) Tj 1.759459 0 Td 52.815315 Tz (with ) Tj 1.437838 0 Td 48.873874 Tz (data ) Tj 1.324324 0 Td 50.45045 Tz (read ) Tj 51.428571 0 0 51.428571 0 1606.236729 Tm 25.297222 0 Td 45.37037 Tz (at ) Tj 1.05 0 Td 38.888889 Tz (1 ) Tj 0.777778 0 Td 55.632716 Tz (minute ) Tj 2.469444 0 Td 45.730453 Tz (intervals ) Tj 2.916667 0 Td 59.953704 Tz (by ) Tj 1.205556 0 Td 51.851852 Tz (a ) Tj 0.797222 0 Td 57.523148 Tz (Synergy2 ) Tj 3.208333 0 Td 55.632716 Tz (system ) Tj 2.508333 0 Td 52.256944 Tz (\(BioTek, ) Tj 51.428571 0 0 51.428571 0 1562.207503 Tm 25.297222 0 Td 55.092593 Tz (Winooski, ) Tj 3.091667 0 Td 42.777778 Tz (Vt.\). ) Tj 1.419444 0 Td 63.734568 Tz (The ) Tj 1.263889 0 Td 50.231481 Tz (fluorescence ) Tj 3.752778 0 Td 56.712963 Tz (produced ) Tj 2.858333 0 Td 59.143519 Tz (upon ) Tj 1.536111 0 Td 50.771605 Tz (the ) Tj 1.030556 0 Td 59.722222 Tz (hydroly ) Tj 51.428571 0 0 51.428571 0 1517.445798 Tm 25.316667 0 Td 41.049383 Tz (sis ) Tj 0.913889 0 Td 58.333333 Tz (of ) Tj 0.797222 0 Td 56.712963 Tz (FS-3 ) Tj 1.575 0 Td 61.574074 Tz (was ) Tj 1.302778 0 Td 55.092593 Tz (monitored ) Tj 3.15 0 Td 52.5 Tz (using ) Tj 1.730556 0 Td 56.712963 Tz (an ) Tj 0.855556 0 Td 47.314815 Tz (excitation ) Tj 3.033333 0 Td 55.092593 Tz (wavelength ) Tj 3.5 0 Td 56.712963 Tz (of ) Tj 51.428571 0 0 51.428571 0 1473.844504 Tm 25.297222 0 Td 59.41358 Tz (485 ) Tj 1.380556 0 Td 74.537037 Tz (nm ) Tj 1.186111 0 Td 58.333333 Tz (and ) Tj 1.302778 0 Td 56.712963 Tz (an ) Tj 0.972222 0 Td 53.472222 Tz (emission ) Tj 2.838889 0 Td 55.740741 Tz (wavelength ) Tj 3.597222 0 Td 59.953704 Tz (of ) Tj 0.875 0 Td 60.493827 Tz (528 ) Tj 1.380556 0 Td 74.537037 Tz (nm ) Tj 1.166667 0 Td 45.37037 Tz (at ) Tj 0.797222 0 Td 56.17284 Tz (37 ) Tj 1.302778 0 Td 53.472222 Tz (C. ) Tj 51.428571 0 0 51.428571 0 1429.587217 Tm 25.316667 0 Td 53.652263 Tz (\(Ferguson ) Tj 3.188889 0 Td 43.75 Tz (et ) Tj 0.797222 0 Td 36.458333 Tz (al., ) Tj 1.166667 0 Td 51.311728 Tz (2006\). ) Tj 2.216667 0 Td 48.611111 Tz (Results ) Tj 2.352778 0 Td 49.691358 Tz (are ) Tj 1.166667 0 Td 61.574074 Tz (shown ) Tj 2.138889 0 Td 45.37037 Tz (at ) Tj 0.797222 0 Td 59.41358 Tz (one ) Tj 1.322222 0 Td 49.907407 Tz (hour, ) Tj 1.75 0 Td 46.990741 Tz (at ) Tj 51.428571 0 0 51.428571 0 1386.005089 Tm 25.277778 0 Td 59.62963 Tz (which ) Tj 2.061111 0 Td 50.555556 Tz (point ) Tj 1.769444 0 Td 41.049383 Tz (all ) Tj 1.030556 0 Td 50.501543 Tz (fluorescence ) Tj 3.908333 0 Td 58.333333 Tz (and ) Tj 1.322222 0 Td 54.768519 Tz (absorbance ) Tj 3.577778 0 Td 55.092593 Tz (changes ) Tj 2.586111 0 Td 51.851852 Tz (as ) Tj 0.894444 0 Td 55.092593 Tz (a ) Tj 51.428571 0 0 51.428571 0 1342.199516 Tm 25.297222 0 Td 50.231481 Tz (function ) Tj 2.566667 0 Td 58.333333 Tz (of ) Tj 0.777778 0 Td 53.472222 Tz (time ) Tj 1.438889 0 Td 58.333333 Tz (were ) Tj 1.536111 0 Td 42.12963 Tz (linear. ) Tj 1.925 0 Td 50.771605 Tz (All ) Tj 1.108333 0 Td 50.231481 Tz (readings ) Tj 2.586111 0 Td 58.333333 Tz (were ) Tj 1.575 0 Td 54.12037 Tz (normalized ) Tj 3.383333 0 Td 45.37037 Tz (to ) Tj 40 0 0 40 0 1305 Tm 32.525 0 Td 64.285714 Tz (vehicle ) Tj 3.225 0 Td 63.095238 Tz (control ) Tj 3.225 0 Td 58.333333 Tz (after ) Tj 2.275 0 Td 62.878788 Tz (subtraction ) Tj 4.725 0 Td 75 Tz (of ) Tj 1.35 0 Td 64.930556 Tz (fluorescence ) Tj 5.225 0 Td 58.333333 Tz (in ) Tj 1.275 0 Td 65.277778 Tz (the ) Tj 40 0 0 40 0 1261 Tm 32.525 0 Td 70.833333 Tz (absence ) Tj 3.15 0 Td 68.75 Tz (of ) Tj 0.925 0 Td 94.791667 Tz (CCM. ) Tj 2.5 0 Td 72.916667 Tz (Data ) Tj 1.875 0 Td 65.277778 Tz (are ) Tj 1.325 0 Td 80 Tz (shown ) Tj 2.55 0 Td 66.666667 Tz (as ) Tj 1 0 Td 62.5 Tz (the ) Tj 1.325 0 Td 76.388889 Tz (meantS.D. ) Tj 4.3 0 Td 68.75 Tz (ofat ) Tj 1.825 0 Td 56.666667 Tz (least ) Tj 51.428571 0 0 51.428571 0 1212.986667 Tm 25.277778 0 Td 49.259259 Tz (three ) Tj 1.652778 0 Td 46.450617 Tz (wells. ) Tj 1.847222 0 Td 50.771605 Tz (All ) Tj 1.069444 0 Td 53.619529 Tz (experiments ) Tj 3.733333 0 Td 58.333333 Tz (were ) Tj 1.594444 0 Td 51.041667 Tz (repeated ) Tj 2.586111 0 Td 46.990741 Tz (at ) Tj 0.719444 0 Td 44.722222 Tz (least ) Tj 1.497222 0 Td 52.5 Tz (twice ) Tj 1.711111 0 Td 61.574074 Tz (and ) Tj 40 0 0 40 0 1174 Tm 32.525 0 Td 57.738095 Tz (results ) Tj 2.65 0 Td 65.277778 Tz (are ) Tj 1.425 0 Td 72.222222 Tz (shown. ) Tj 51.428571 0 0 51.428571 0 1124.8 Tm 25.297222 0 Td 78.858025 Tz (ATX ) Tj 1.633333 0 Td 49.421296 Tz (Kinetics ) Tj 2.547222 0 Td 56.712963 Tz (Assays ) Tj 51.428571 0 0 51.428571 0 1083.105395 Tm 26.016667 0 Td 77.777778 Tz (ATX ) Tj 1.594444 0 Td 46.990741 Tz (kinetics ) Tj 2.45 0 Td 51.851852 Tz (assays ) Tj 2.041667 0 Td 58.333333 Tz (were ) Tj 1.575 0 Td 56.17284 Tz (performed ) Tj 3.208333 0 Td 52.5 Tz (using ) Tj 1.75 0 Td 49.259259 Tz (eight ) Tj 1.652778 0 Td 46.090535 Tz (different ) Tj 40 0 0 40 0 1043 Tm 32.525 0 Td 64.880952 Tz (concentrations ) Tj 5.7 0 Td 72.916667 Tz (of ) Tj 1.025 0 Td 62.037037 Tz (Substrate ) Tj 3.575 0 Td 76.388889 Tz (and ) Tj 1.6 0 Td 76.388889 Tz (two ) Tj 1.675 0 Td 59.259259 Tz (different ) Tj 3.45 0 Td 64.583333 Tz (concentrations ) Tj 51.428571 0 0 51.428571 0 994.004831 Tm 25.297222 0 Td 58.333333 Tz (of ) Tj 0.777778 0 Td 46.8107 Tz (inhibitor ) Tj 2.663889 0 Td 57.523148 Tz (\(ChemBridge, ) Tj 4.336111 0 Td 58.333333 Tz (San ) Tj 1.263889 0 Td 52.932099 Tz (Diego, ) Tj 2.080556 0 Td 42.534722 Tz (Calif.\). ) Tj 2.216667 0 Td 62.654321 Tz (The ) Tj 1.302778 0 Td 57.523148 Tz (FS-3 ) Tj 1.594444 0 Td 68.055556 Tz (sub ) Tj 51.428571 0 0 51.428571 0 949.869063 Tm 25.316667 0 Td 43.209877 Tz (strate ) Tj 1.711111 0 Td 50.694444 Tz (concentrations ) Tj 4.491667 0 Td 54.012346 Tz (ranged ) Tj 2.119444 0 Td 58.333333 Tz (from ) Tj 1.594444 0 Td 51.311728 Tz (20-0.3 ) Tj 2.1 0 Td 81.018519 Tz (uM ) Tj 1.166667 0 Td 58.333333 Tz (on ) Tj 0.894444 0 Td 48.611111 Tz (the ) Tj 1.05 0 Td 44.290123 Tz (plate. ) Tj 51.428571 0 0 51.428571 0 905.02716 Tm 26.016667 0 Td 63.734568 Tz (The ) Tj 1.283333 0 Td 53.796296 Tz (normalized ) Tj 3.363889 0 Td 50.501543 Tz (fluorescence ) Tj 3.772222 0 Td 43.981481 Tz (results ) Tj 1.983333 0 Td 59.143519 Tz (were ) Tj 1.516667 0 Td 48.148148 Tz (plotted ) Tj 2.119444 0 Td 50.231481 Tz (as ) Tj 0.738889 0 Td 55.092593 Tz (a ) Tj 0.447222 0 Td 63.194444 Tz (func ) Tj 40 0 0 40 0 868 Tm 32.5 0 Td 60.416667 Tz (tion ) Tj 1.675 0 Td 68.75 Tz (of ) Tj 0.925 0 Td 68.75 Tz (time ) Tj 1.85 0 Td 56.25 Tz (in ) Tj 0.875 0 Td 66.666667 Tz (order ) Tj 2.1 0 Td 60.416667 Tz (to ) Tj 0.925 0 Td 69.444444 Tz (determine ) Tj 3.9 0 Td 51.785714 Tz (initial ) Tj 2.375 0 Td 54.166667 Tz (rates. ) Tj 2.125 0 Td 80.555556 Tz (The ) Tj 1.65 0 Td 51.190476 Tz (initial ) Tj 2.35 0 Td 57.5 Tz (rates ) Tj 51.428571 0 0 51.428571 0 819.007101 Tm 25.277778 0 Td 59.953704 Tz (were ) Tj 1.555556 0 Td 48.611111 Tz (plotted ) Tj 2.177778 0 Td 49.537037 Tz (against ) Tj 2.197222 0 Td 50.771605 Tz (the ) Tj 1.05 0 Td 47.890947 Tz (Substrate ) Tj 2.722222 0 Td 50.605413 Tz (concentration ) Tj 4.083333 0 Td 59.41358 Tz (and ) Tj 1.205556 0 Td 55.092593 Tz (a ) Tj 0.466667 0 Td 56.17284 Tz (rectan ) Tj 51.428571 0 0 51.428571 0 776.539528 Tm 25.297222 0 Td 50.555556 Tz (gular ) Tj 1.886111 0 Td 51.527778 Tz (hyperbolic ) Tj 3.5 0 Td 53.796296 Tz (curve ) Tj 2.002778 0 Td 61.574074 Tz (was ) Tj 1.497222 0 Td 41.049383 Tz (fitted ) Tj 1.866667 0 Td 46.990741 Tz (to ) Tj 0.952778 0 Td 50.771605 Tz (the ) Tj 1.302778 0 Td 51.041667 Tz (data ) Tj 1.594444 0 Td 53.148148 Tz (using ) Tj 1.963889 0 Td 50.771605 Tz (the ) Tj 51.428571 0 0 51.428571 0 734.763819 Tm 25.316667 0 Td 56.17284 Tz (KaleidaGraph ) Tj 4.433333 0 Td 51.851852 Tz (software ) Tj 2.819444 0 Td 55.092593 Tz (\(Synergy ) Tj 3.033333 0 Td 50.771605 Tz (Software, ) Tj 3.188889 0 Td 52.662037 Tz (Reading, ) Tj 2.916667 0 Td 42.939815 Tz (Pa., ) Tj 51.428571 0 0 51.428571 0 686 Tm 25.297222 0 Td 52.777778 Tz (Version ) Tj 2.488889 0 Td 46.450617 Tz (4.03\). ) Tj 1.944444 0 Td 62.654321 Tz (The ) Tj 1.419444 0 Td 84.259259 Tz (K ) Tj 1.166667 0 Td 58.333333 Tz (and ) Tj 1.283333 0 Td 51.851852 Tz (V, ) Tj 1.730556 0 Td 58.333333 Tz (were ) Tj 1.633333 0 Td 49.259259 Tz (calculated ) Tj 3.247222 0 Td 57.523148 Tz (from ) Tj 1.652778 0 Td 50.771605 Tz (the ) Tj 51.428571 0 0 51.428571 0 644.055758 Tm 25.297222 0 Td 47.170782 Tz (resulting ) Tj 2.722222 0 Td 43.75 Tz (plots. ) Tj 1.788889 0 Td 71.296296 Tz (Mode ) Tj 1.886111 0 Td 58.333333 Tz (of ) Tj 0.797222 0 Td 46.990741 Tz (inhibition ) Tj 3.013889 0 Td 60.493827 Tz (was ) Tj 1.302778 0 Td 54.444444 Tz (determined ) Tj 3.461111 0 Td 59.143519 Tz (from ) Tj 1.594444 0 Td 50.771605 Tz (the ) Tj 52.857143 0 0 52.857143 0 598 Tm 24.613514 0 Td 45.545546 Tz (inhibitor ) Tj 2.554054 0 Td 45.195195 Tz (effect ) Tj 1.778378 0 Td 55.18018 Tz (on ) Tj 0.832432 0 Td 74.099099 Tz (K, ) Tj 1.040541 0 Td 56.756757 Tz (and ) Tj 1.135135 0 Td 81.981982 Tz (V ) Tj 1.57027 0 Td 45.495495 Tz (values. ) Tj 2.062162 0 Td 62.012012 Tz (The ) Tj 1.267568 0 Td 46.509009 Tz (dissociation ) Tj 3.518919 0 Td 68.318318 Tz (con ) Tj 51.428571 0 0 51.428571 0 556.117861 Tm 25.316667 0 Td 44.722222 Tz (stant ) Tj 1.516667 0 Td 64.814815 Tz (\(K\) ) Tj 1.322222 0 Td 48.611111 Tz (for ) Tj 1.030556 0 Td 46.450617 Tz (inhibitor ) Tj 2.644444 0 Td 53.240741 Tz (binding ) Tj 2.411111 0 Td 60.493827 Tz (was ) Tj 1.263889 0 Td 49.259259 Tz (calculated ) Tj 3.091667 0 Td 50.771605 Tz (for ) Tj 1.011111 0 Td 54.282407 Tz (each ) Tj 1.477778 0 Td 58.333333 Tz (of ) Tj 0.777778 0 Td 50.771605 Tz (the ) Tj 51.428571 0 0 51.428571 0 513.135338 Tm 25.297222 0 Td 44.781145 Tz (inhibitors. ) Tj 3.305556 0 Td 53.472222 Tz (K, ) Tj 1.011111 0 Td 47.530864 Tz (for ) Tj 1.147222 0 Td 53.098291 Tz (uncompetitive ) Tj 4.452778 0 Td 46.990741 Tz (inhibition ) Tj 3.15 0 Td 62.654321 Tz (was ) Tj 1.438889 0 Td 49.583333 Tz (calculated ) Tj 51.428571 0 0 51.428571 0 472.564295 Tm 25.277778 0 Td 53.148148 Tz (using ) Tj 1.808333 0 Td 53.472222 Tz (Equation ) Tj 2.8 0 Td 32.407407 Tz (1 ) Tj 0.447222 0 Td 59.41358 Tz (\(Cheng ) Tj 2.294444 0 Td 58.333333 Tz (and ) Tj 1.244444 0 Td 46.585648 Tz (Prusoff, ) Tj 2.508333 0 Td 49.151235 Tz (1973\). ) Tj 1.983333 0 Td 53.877315 Tz (Equation ) Tj 2.780556 0 Td 55.092593 Tz (2 ) Tj 0.505556 0 Td 61.574074 Tz (was ) Tj 51.428571 0 0 51.428571 0 426.835821 Tm 25.277778 0 Td 55.902778 Tz (used ) Tj 1.613889 0 Td 46.450617 Tz (for ) Tj 1.05 0 Td 51.851852 Tz (competitive ) Tj 3.655556 0 Td 46.990741 Tz (inhibition ) Tj 3.091667 0 Td 58.873457 Tz (\(Cheng ) Tj 2.352778 0 Td 59.41358 Tz (and ) Tj 1.322222 0 Td 46.990741 Tz (Prusoff, ) Tj 2.605556 0 Td 49.151235 Tz (1973\). ) Tj 51.428571 0 0 51.428571 0 381.17 Tm 25.297222 0 Td 63.734568 Tz (The ) Tj 1.244444 0 Td 54.166667 Tz (average ) Tj 2.430556 0 Td 47.530864 Tz (substrate ) Tj 2.741667 0 Td 84.259259 Tz (K ) Tj 1.088889 0 Td 46.759259 Tz (values, ) Tj 2.1 0 Td 53.472222 Tz (3.7+/- ) Tj 2.002778 0 Td 45.37037 Tz (1.9 ) Tj 1.166667 0 Td 68.055556 Tz (LM ) Tj 0.972222 0 Td 50.925926 Tz (\(n=22\), ) Tj 2.313889 0 Td 58.333333 Tz (were ) Tj 52.857143 0 0 52.857143 0 337.622166 Tm 24.613514 0 Td 47.927928 Tz (calculated ) Tj 3.102703 0 Td 51.081081 Tz (using ) Tj 1.721622 0 Td 48.348348 Tz (the ) Tj 1.078378 0 Td 47.297297 Tz (individual ) Tj 3.083784 0 Td 78.828829 Tz (K ) Tj 1.097297 0 Td 48.873874 Tz (values ) Tj 2.005405 0 Td 52.657658 Tz (determined ) Tj 3.386486 0 Td 50.45045 Tz (using ) Tj 51.428571 0 0 51.428571 0 298.742621 Tm 25.297222 0 Td 50.084175 Tz (rectangular ) Tj 3.402778 0 Td 51.527778 Tz (hyperbolic ) Tj 3.247222 0 Td 53.796296 Tz (curve ) Tj 1.769444 0 Td 40.740741 Tz (fitting ) Tj 1.827778 0 Td 56.712963 Tz (of ) Tj 0.758333 0 Td 46.666667 Tz (plots ) Tj 1.555556 0 Td 56.712963 Tz (of ) Tj 0.758333 0 Td 39.814815 Tz (initial ) Tj 1.827778 0 Td 48.206019 Tz (velocity ) Tj 51.428571 0 0 51.428571 0 252.205219 Tm 25.297222 0 Td 50.771605 Tz (Versus ) Tj 2.002778 0 Td 47.530864 Tz (Substrate ) Tj 2.741667 0 Td 50.356125 Tz (concentration ) Tj 4.083333 0 Td 58.333333 Tz (from ) Tj 1.575 0 Td 55.092593 Tz (of ) Tj 0.738889 0 Td 39.969136 Tz (all ) Tj 0.875 0 Td 46.990741 Tz (inhibition ) Tj 2.975 0 Td 51.446759 Tz (analyses ) Tj 51.428571 0 0 51.428571 0 210 Tm 25.297222 0 Td 49.691358 Tz (for ) Tj 1.088889 0 Td 51.851852 Tz (FS-3. ) Tj 1.827778 0 Td 55.092593 Tz (For ) Tj 1.225 0 Td 58.981481 Tz (mixed ) Tj 2.002778 0 Td 67.24537 Tz (mode ) Tj 1.827778 0 Td 46.666667 Tz (inhibition ) Tj 3.052778 0 Td 75.833333 Tz (KICso ) Tj 2.605556 0 Td 61.574074 Tz (was ) Tj 1.322222 0 Td 60.185185 Tz (assumed ) Tj 51.428571 0 0 51.428571 0 171.036145 Tm 25.316667 0 Td 55.681818 Tz (\(Burlingham ) Tj 3.869444 0 Td 59.41358 Tz (and ) Tj 1.244444 0 Td 51.851852 Tz (Widlanski, ) Tj 3.325 0 Td 50.771605 Tz (2003\). ) Tj ET Q endstream endobj 296 0 obj << /Length 1 >> stream q endstream endobj 297 0 obj << /Length 29348 >> stream Q q 0.24 0 0 0.24 0 0 cm BT /F1 1 Tf 3 Tr 62.857143 0 0 62.857143 0 3023 Tm 17.325 0 Td 83.522727 Tz (US ) Tj 1.240909 0 Td 57.154882 Tz (8,497,371 ) Tj 3.388636 0 Td 74.242424 Tz (B2 ) Tj 51.428571 0 0 51.428571 0 2969 Tm 14.602778 0 Td 76.157407 Tz (21 ) Tj 62.380952 0 0 62.380952 0 2860.510067 Tm 10.227481 0 Td 58.778626 Tz (K ) Tj 0.577099 0 Td 50.763359 Tz (= ) Tj 0.448855 0 Td 40.076336 Tz (- ) Tj 1.250382 0 Td 50.763359 Tz (2 ) Tj 0.545038 0 Td 112.21374 Tz (- ) Tj 5.979389 0 Td 28.498728 Tz (\(1\) ) Tj 38.571429 0 0 38.571429 0 2831 Tm 18.277778 0 Td 43.209877 Tz (1 ) Tj 0.518519 0 Td 69.135802 Tz (+ ) Tj 0.596296 0 Td 83.539095 Tz (\(Kf ) Tj 1.866667 0 Td 75.617284 Tz (S\) ) Tj 30 0 0 30 0 2768.380952 Tm 22.433333 0 Td 22.222222 Tz (: ) Tj 2.766667 0 Td 66.666667 Tz (IC50 ) Tj 14.366667 0 Td 59.259259 Tz (\(2\) ) Tj 51.428571 0 0 51.428571 0 2723 Tm 13.708333 0 Td 32.407407 Tz (1 ) Tj 0.369444 0 Td 55.092593 Tz (+ ) Tj 0.466667 0 Td 49.537037 Tz (\(SI/K.\) ) Tj 51.428571 0 0 51.428571 0 2616.166134 Tm 6.358333 0 Td 78.858025 Tz (ATX ) Tj 1.633333 0 Td 52.824074 Tz (Expression ) Tj 3.344444 0 Td 49.907407 Tz (Tests ) Tj 40 0 0 40 0 2576 Tm 9.125 0 Td 92.916667 Tz (MDA-MB-435 ) Tj 6.1 0 Td 56.666667 Tz (cells ) Tj 2.225 0 Td 75 Tz (were ) Tj 2.3 0 Td 63.020833 Tz (cultured ) Tj 3.575 0 Td 54.166667 Tz (at ) Tj 1.125 0 Td 72.222222 Tz (37 ) Tj 1.825 0 Td 66.666667 Tz (C. ) Tj 1.375 0 Td 70.833333 Tz (under ) Tj 2.575 0 Td 70.833333 Tz (a ) Tj 51.428571 0 0 51.428571 0 2527.363636 Tm 6.338889 0 Td 53.148148 Tz (humidified ) Tj 3.441667 0 Td 56.388889 Tz (atmosphere ) Tj 3.655556 0 Td 51.527778 Tz (containing ) Tj 3.402778 0 Td 76.157407 Tz (5% ) Tj 1.205556 0 Td 85.87963 Tz (CO ) Tj 1.633333 0 Td 42.12963 Tz (in ) Tj 0.855556 0 Td 54.768519 Tz (Dulbecco's ) Tj 51.428571 0 0 51.428571 0 2481.820766 Tm 6.358333 0 Td 55.902778 Tz (Modified ) Tj 2.994444 0 Td 53.796296 Tz (Eagle ) Tj 1.963889 0 Td 66.975309 Tz (Medium ) Tj 2.761111 0 Td 75.617284 Tz (\(DMEM\) ) Tj 3.052778 0 Td 55.092593 Tz (\(MediaTech, ) Tj 4.005556 0 Td 55.497685 Tz (Herndon, ) Tj 51.428571 0 0 51.428571 0 2442.618469 Tm 6.358333 0 Td 50.231481 Tz (Va.\) ) Tj 1.341667 0 Td 51.527778 Tz (containing ) Tj 3.305556 0 Td 58.333333 Tz (100 ) Tj 1.205556 0 Td 60.763889 Tz (U/ml ) Tj 1.633333 0 Td 44.191919 Tz (penicillin, ) Tj 3.15 0 Td 58.333333 Tz (100 ) Tj 1.458333 0 Td 58.333333 Tz (g/ml ) Tj 1.575 0 Td 53.20216 Tz (streptomycin ) Tj 51.428571 0 0 51.428571 0 2397.160494 Tm 6.377778 0 Td 52.932099 Tz (\(Hyclone, ) Tj 3.091667 0 Td 55.632716 Tz (Logan, ) Tj 2.216667 0 Td 50.231481 Tz (Utah\), ) Tj 2.041667 0 Td 76.157407 Tz (5% ) Tj 1.127778 0 Td 43.425926 Tz (fetal ) Tj 1.477778 0 Td 55.092593 Tz (bovine ) Tj 2.177778 0 Td 58.333333 Tz (serum ) Tj 1.983333 0 Td 58.981481 Tz (\(FBS\) ) Tj 1.963889 0 Td 75.617284 Tz (\(Hy ) Tj 51.428571 0 0 51.428571 0 2354.631016 Tm 6.358333 0 Td 48.611111 Tz (clone, ) Tj 2.177778 0 Td 55.632716 Tz (Logan, ) Tj 2.411111 0 Td 50.231481 Tz (Utah\), ) Tj 2.197222 0 Td 59.41358 Tz (and ) Tj 1.477778 0 Td 55.092593 Tz (2 ) Tj 0.758333 0 Td 97.222222 Tz (mM ) Tj 1.613889 0 Td 53.914141 Tz (L-glutamine ) Tj 3.947222 0 Td 52.932099 Tz (\(Hyclone, ) Tj 51.428571 0 0 51.428571 0 2310.683636 Tm 6.377778 0 Td 56.17284 Tz (Logan, ) Tj 2.158333 0 Td 50.771605 Tz (Utah\). ) Tj 2.002778 0 Td 66.435185 Tz (Upon ) Tj 1.769444 0 Td 51.851852 Tz (reaching ) Tj 2.625 0 Td 61.574074 Tz (80 ) Tj 0.875 0 Td 45.37037 Tz (to ) Tj 0.7 0 Td 73.45679 Tz (95% ) Tj 1.497222 0 Td 49.789562 Tz (confluency, ) Tj 3.480556 0 Td 48.611111 Tz (the ) Tj 0.991667 0 Td 44.722222 Tz (cells ) Tj 51.428571 0 0 51.428571 0 2266.539623 Tm 6.338889 0 Td 59.953704 Tz (were ) Tj 1.711111 0 Td 59.953704 Tz (washed ) Tj 2.488889 0 Td 51.851852 Tz (twice ) Tj 1.847222 0 Td 52.662037 Tz (with ) Tj 1.575 0 Td 42.12963 Tz (sterile ) Tj 2.022222 0 Td 55.092593 Tz (phosphate ) Tj 3.247222 0 Td 51.041667 Tz (buffered ) Tj 2.722222 0 Td 43.981481 Tz (saline. ) Tj 51.428571 0 0 51.428571 0 2226.285714 Tm 6.377778 0 Td 54.444444 Tz (Serum-free ) Tj 3.538889 0 Td 92.361111 Tz (DMEM ) Tj 2.430556 0 Td 51.527778 Tz (containing ) Tj 3.344444 0 Td 54.79798 Tz (L-glutamine ) Tj 3.791667 0 Td 60.493827 Tz (and ) Tj 1.283333 0 Td 46.254209 Tz (antibiotics ) Tj 40 0 0 40 0 2189 Tm 8.15 0 Td 80.555556 Tz (was ) Tj 1.675 0 Td 65.625 Tz (then ) Tj 1.75 0 Td 75 Tz (added ) Tj 2.425 0 Td 60.416667 Tz (to ) Tj 0.925 0 Td 63.888889 Tz (the ) Tj 1.3 0 Td 53.472222 Tz (cells. ) Tj 2.1 0 Td 70.833333 Tz (Conditioned ) Tj 4.875 0 Td 75 Tz (media ) Tj 2.425 0 Td 79.166667 Tz (was ) Tj 1.6 0 Td 63.888889 Tz (collected ) Tj 40 0 0 40 0 2148 Tm 8.175 0 Td 58.333333 Tz (after ) Tj 1.875 0 Td 73.333333 Tz (36-48 ) Tj 2.4 0 Td 68.333333 Tz (hours ) Tj 2.275 0 Td 70.833333 Tz (of ) Tj 0.925 0 Td 65.833333 Tz (incubation ) Tj 4.15 0 Td 67.708333 Tz (with ) Tj 1.825 0 Td 67.916667 Tz (serum-free ) Tj 4.3 0 Td 101.666667 Tz (DMEM. ) Tj 3.25 0 Td 81.944444 Tz (The ) Tj 51.428571 0 0 51.428571 0 2099.529271 Tm 6.358333 0 Td 58.981481 Tz (media ) Tj 1.944444 0 Td 60.493827 Tz (was ) Tj 1.244444 0 Td 51.851852 Tz (concentrated ) Tj 3.927778 0 Td 60.763889 Tz (~10x ) Tj 1.613889 0 Td 58.333333 Tz (and ) Tj 1.166667 0 Td 50.231481 Tz (buffer ) Tj 1.905556 0 Td 57.613169 Tz (exchanged ) Tj 3.266667 0 Td 46.180556 Tz (into ) Tj 1.244444 0 Td 47.800926 Tz (Tris ) Tj 51.428571 0 0 51.428571 0 2062.113924 Tm 6.377778 0 Td 54.012346 Tz (\(50 ) Tj 1.205556 0 Td 75.617284 Tz (mM, ) Tj 1.575 0 Td 76.157407 Tz (pH ) Tj 1.147222 0 Td 48.611111 Tz (7.4\) ) Tj 1.380556 0 Td 51.203704 Tz (containing ) Tj 3.325 0 Td 72.376543 Tz (20% ) Tj 1.536111 0 Td 51.446759 Tz (ethylene ) Tj 2.702778 0 Td 50.231481 Tz (glycol ) Tj 2.061111 0 Td 51.851852 Tz (using ) Tj 1.788889 0 Td 61.574074 Tz (30 ) Tj 51.428571 0 0 51.428571 0 2018.969072 Tm 6.358333 0 Td 66.975309 Tz (kDa ) Tj 1.633333 0 Td 54.012346 Tz (molecular ) Tj 3.305556 0 Td 55.092593 Tz (weight ) Tj 2.372222 0 Td 50.771605 Tz (cutoff ) Tj 2.119444 0 Td 39.351852 Tz (filters ) Tj 2.061111 0 Td 48.021886 Tz (\(Millipore, ) Tj 3.616667 0 Td 48.611111 Tz (Beverly, ) Tj 51.428571 0 0 51.428571 0 1977.914081 Tm 6.358333 0 Td 54.552469 Tz (Mass.\) ) Tj 2.119444 0 Td 43.75 Tz (in ) Tj 0.661111 0 Td 59.953704 Tz (an ) Tj 0.816667 0 Td 65.462963 Tz (Amico ) Tj 2.119444 0 Td 50.636574 Tz (pressure ) Tj 2.566667 0 Td 42.939815 Tz (cell ) Tj 1.186111 0 Td 48.021886 Tz (\(Millipore, ) Tj 3.344444 0 Td 49.421296 Tz (Beverly, ) Tj 2.508333 0 Td 50.462963 Tz (Mass.\). ) Tj 51.428571 0 0 51.428571 0 1933.356291 Tm 6.358333 0 Td 51.851852 Tz (Aliquots ) Tj 2.683333 0 Td 58.333333 Tz (of ) Tj 0.855556 0 Td 58.333333 Tz (10x ) Tj 1.244444 0 Td 52.146465 Tz (conditioned ) Tj 3.655556 0 Td 57.685185 Tz (media ) Tj 1.925 0 Td 59.953704 Tz (were ) Tj 1.594444 0 Td 49.691358 Tz (stored ) Tj 1.944444 0 Td 46.990741 Tz (at ) Tj 0.719444 0 Td 61.574074 Tz (4C. ) Tj 40 0 0 40 0 1898 Tm 8.2 0 Td 68.910256 Tz (Determination ) Tj 5.625 0 Td 70.833333 Tz (of ) Tj 1 0 Td 90.625 Tz (NPP6 ) Tj 2.425 0 Td 73.611111 Tz (and ) Tj 1.6 0 Td 89.583333 Tz (NPP7 ) Tj 2.45 0 Td 61.25 Tz (Inhibition ) Tj 51.428571 0 0 51.428571 0 1855.18226 Tm 7.116667 0 Td 47.170782 Tz (Inhibitor ) Tj 2.683333 0 Td 44.486532 Tz (selectivity ) Tj 3.111111 0 Td 60.493827 Tz (was ) Tj 1.205556 0 Td 54.62963 Tz (assayed ) Tj 2.45 0 Td 52.5 Tz (using ) Tj 1.691667 0 Td 54.520697 Tz (p-nitrophenylphos ) Tj 51.428571 0 0 51.428571 0 1812.744325 Tm 6.358333 0 Td 51.157407 Tz (phoryl-choline ) Tj 4.491667 0 Td 63.425926 Tz (\(pNPPC\) ) Tj 2.838889 0 Td 52.5 Tz (\(Sigma-Aldrich, ) Tj 4.919444 0 Td 42.12963 Tz (St. ) Tj 0.991667 0 Td 50.231481 Tz (Louis, ) Tj 2.022222 0 Td 58.333333 Tz (Mo.\) ) Tj 1.575 0 Td 51.851852 Tz (as ) Tj 51.428571 0 0 51.428571 0 1766 Tm 6.377778 0 Td 47.530864 Tz (substrate ) Tj 2.877778 0 Td 48.611111 Tz (for ) Tj 1.166667 0 Td 70.486111 Tz (NPP6 ) Tj 1.983333 0 Td 59.41358 Tz (and ) Tj 1.380556 0 Td 61.574074 Tz (NPP7. ) Tj 2.138889 0 Td 65.895062 Tz (The ) Tj 1.477778 0 Td 42.777778 Tz (final ) Tj 1.633333 0 Td 59.953704 Tz (volume ) Tj 2.45 0 Td 55.092593 Tz (\(60 ) Tj 1.322222 0 Td 56.17284 Tz (uL\) ) Tj 51.428571 0 0 51.428571 0 1724 Tm 6.358333 0 Td 51.851852 Tz (included ) Tj 2.683333 0 Td 61.574074 Tz (20 ) Tj 0.952778 0 Td 64.814815 Tz (uL ) Tj 0.952778 0 Td 64.814815 Tz (\(CM, ) Tj 1.769444 0 Td 69.675926 Tz (NPP6 ) Tj 1.886111 0 Td 50.231481 Tz (or ) Tj 0.758333 0 Td 73.726852 Tz (CCM, ) Tj 1.983333 0 Td 62.222222 Tz (NPP7, ) Tj 2.061111 0 Td 61.574074 Tz (20 ) Tj 0.952778 0 Td 64.814815 Tz (uL ) Tj 0.952778 0 Td 47.170782 Tz (inhibitor ) Tj 51.428571 0 0 51.428571 0 1685.412005 Tm 6.377778 0 Td 54.012346 Tz (\(10 ) Tj 1.283333 0 Td 79.398148 Tz (uM ) Tj 1.263889 0 Td 50.411523 Tz (including ) Tj 3.072222 0 Td 72.916667 Tz (1% ) Tj 1.225 0 Td 77.12963 Tz (DMSO\) ) Tj 2.566667 0 Td 46.990741 Tz (in ) Tj 0.836111 0 Td 52.5 Tz (assay ) Tj 1.866667 0 Td 44.907407 Tz (buffer, ) Tj 2.177778 0 Td 59.41358 Tz (and ) Tj 1.341667 0 Td 61.574074 Tz (20 ) Tj 1.225 0 Td 48.611111 Tz (LL ) Tj 52.857143 0 0 52.857143 0 1642.047493 Tm 6.167568 0 Td 71.261261 Tz (pNPPC ) Tj 2.402703 0 Td 52.552553 Tz (\(10 ) Tj 1.210811 0 Td 73.573574 Tz (mM, ) Tj 1.589189 0 Td 68.581081 Tz (NPP6 ) Tj 1.872973 0 Td 55.18018 Tz (or ) Tj 0.927027 0 Td 37.837838 Tz (1 ) Tj 0.548649 0 Td 63.063063 Tz (NPP7\) ) Tj 2.156757 0 Td 44.144144 Tz (in ) Tj 0.775676 0 Td 51.081081 Tz (assay ) Tj 1.797297 0 Td 42.792793 Tz (buffer. ) Tj 2.081081 0 Td 68.581081 Tz (NPP6 ) Tj 51.428571 0 0 51.428571 0 1598.782396 Tm 6.358333 0 Td 51.851852 Tz (assay ) Tj 1.769444 0 Td 49.691358 Tz (buffer ) Tj 1.925 0 Td 52.932099 Tz (contained ) Tj 3.052778 0 Td 61.574074 Tz (500 ) Tj 1.322222 0 Td 66.975309 Tz (mM. ) Tj 1.4 0 Td 55.740741 Tz (NaCl, ) Tj 1.905556 0 Td 62.222222 Tz (0.05% ) Tj 2.022222 0 Td 50.771605 Tz (Triton ) Tj 2.022222 0 Td 56.17284 Tz (X-100, ) Tj 51.428571 0 0 51.428571 0 1558.34487 Tm 6.416667 0 Td 58.333333 Tz (100 ) Tj 1.225 0 Td 97.222222 Tz (mM ) Tj 1.322222 0 Td 54.6875 Tz (Tris-HCl ) Tj 2.838889 0 Td 60.493827 Tz (\(pH ) Tj 1.283333 0 Td 43.425926 Tz (9.0\), ) Tj 1.516667 0 Td 56.481481 Tz (whereas ) Tj 2.566667 0 Td 69.675926 Tz (NPP7 ) Tj 1.866667 0 Td 51.851852 Tz (assay ) Tj 1.75 0 Td 49.151235 Tz (buffer ) Tj 1.905556 0 Td 62.654321 Tz (was ) Tj 51.428571 0 0 51.428571 0 1516.97786 Tm 6.358333 0 Td 56.17284 Tz (comprised ) Tj 3.169444 0 Td 56.712963 Tz (of ) Tj 0.758333 0 Td 56.712963 Tz (50 ) Tj 0.836111 0 Td 100.462963 Tz (mM ) Tj 1.322222 0 Td 47.800926 Tz (Tris ) Tj 1.322222 0 Td 55.902778 Tz (HCl, ) Tj 1.497222 0 Td 72.916667 Tz (pH ) Tj 0.991667 0 Td 46.180556 Tz (8.5, ) Tj 1.322222 0 Td 56.17284 Tz (150 ) Tj 1.166667 0 Td 72.222222 Tz (mMNaCl, ) Tj 3.169444 0 Td 58.333333 Tz (and ) Tj 1.263889 0 Td 53.472222 Tz (10 ) Tj 51.428571 0 0 51.428571 0 1475.438424 Tm 6.358333 0 Td 100.462963 Tz (mM ) Tj 1.458333 0 Td 49.200337 Tz (taurocholic ) Tj 3.480556 0 Td 45.37037 Tz (acid. ) Tj 1.633333 0 Td 57.523148 Tz (However, ) Tj 2.994444 0 Td 50.231481 Tz (unlike ) Tj 2.041667 0 Td 49.691358 Tz (the ) Tj 1.108333 0 Td 52.572016 Tz (published ) Tj 3.072222 0 Td 69.675926 Tz (meth ) Tj 51.428571 0 0 51.428571 0 1433.715663 Tm 6.358333 0 Td 48.611111 Tz (ods, ) Tj 1.341667 0 Td 76.157407 Tz (EDTA ) Tj 1.944444 0 Td 62.654321 Tz (was ) Tj 1.263889 0 Td 51.851852 Tz (not ) Tj 1.030556 0 Td 57.685185 Tz (added ) Tj 1.827778 0 Td 46.990741 Tz (to ) Tj 0.719444 0 Td 48.611111 Tz (the ) Tj 0.972222 0 Td 70.486111 Tz (NPP7 ) Tj 1.788889 0 Td 53.796296 Tz (assay ) Tj 1.711111 0 Td 44.444444 Tz (buffer. ) Tj 1.983333 0 Td 49.691358 Tz (All ) Tj 1.030556 0 Td 51.311728 Tz (assays ) Tj 31.428571 0 0 31.428571 0 1242 Tm 37.609091 0 Td 106.060606 Tz (HOOC ) Tj 40 0 0 40 0 699.179487 Tm 29.175 0 Td 48.611111 Tz (Substitution ) Tj 3.7 0 Td 60.416667 Tz (on ) Tj 0.95 0 Td 79.166667 Tz (D ) Tj 0.7 0 Td 47.916667 Tz (ring ) Tj 45.714286 0 0 45.714286 0 637 Tm 24.171875 0 Td 53.846154 Tz (LEAD-Dichloro ) Tj 4.353125 0 Td 69.270833 Tz (\(R,R\) ) Tj 48.571429 0 0 48.571429 0 562.330128 Tm 22.420588 0 Td 44.150327 Tz (Trifluoromethyl ) Tj 4.117647 0 Td 51.041667 Tz (\(meta-R\) ) Tj 45.714286 0 0 45.714286 0 476 Tm 25.134375 0 Td 46.940104 Tz (Dichloro ) Tj 2.45 0 Td 42.838542 Tz (\(R', ) Tj 1.225 0 Td 71.09375 Tz (R\) ) Tj 48.571429 0 0 48.571429 0 395 Tm 23.861765 0 Td 48.039216 Tz (Iodo ) Tj 1.276471 0 Td 51.470588 Tz (\(meta-R\) ) Tj 45.714286 0 0 45.714286 0 313 Tm 25.15625 0 Td 48.611111 Tz (Chloro ) Tj 1.925 0 Td 53.320312 Tz (\(meta-R\) ) Tj 48.571429 0 0 48.571429 0 230 Tm 23.244118 0 Td 43.983957 Tz (Thiadiazole ) Tj 3.026471 0 Td 65.882353 Tz (\(R,R\) ) Tj 30 0 0 30 0 2547 Tm 41.666667 0 Td 75 Tz (10 ) Tj 30 0 0 30 0 2339 Tm 41.666667 0 Td 72.222222 Tz (15 ) Tj 30 0 0 30 0 1923 Tm 41.6 0 Td 77.777778 Tz (25 ) Tj 30 0 0 30 0 1716 Tm 41.6 0 Td 80.555556 Tz (30 ) Tj 30 0 0 30 0 1507 Tm 41.6 0 Td 77.777778 Tz (35 ) Tj 51.428571 0 0 51.428571 0 2969 Tm 33.541667 0 Td 77.777778 Tz (22 ) Tj 51.428571 0 0 51.428571 0 2916.823899 Tm 25.277778 0 Td 59.953704 Tz (were ) Tj 1.672222 0 Td 56.532922 Tz (performed ) Tj 3.305556 0 Td 46.990741 Tz (in ) Tj 0.816667 0 Td 50.231481 Tz (96-well, ) Tj 2.683333 0 Td 51.851852 Tz (half ) Tj 1.4 0 Td 49.421296 Tz (area ) Tj 1.438889 0 Td 47.530864 Tz (plates ) Tj 2.002778 0 Td 54.6875 Tz (\(Corning ) Tj 2.916667 0 Td 40.833333 Tz (Inc., ) Tj 51.428571 0 0 51.428571 0 2874 Tm 25.316667 0 Td 52.314815 Tz (Lowell, ) Tj 2.527778 0 Td 54.012346 Tz (Mass.\) ) Tj 2.236111 0 Td 45.37037 Tz (at ) Tj 0.836111 0 Td 55.092593 Tz (37 ) Tj 1.302778 0 Td 55.092593 Tz (C. ) Tj 1.011111 0 Td 52.662037 Tz (with ) Tj 1.594444 0 Td 49.421296 Tz (data ) Tj 1.497222 0 Td 48.611111 Tz (collected ) Tj 2.897222 0 Td 46.990741 Tz (at ) Tj 0.875 0 Td 58.333333 Tz (2 ) Tj 0.661111 0 Td 56.17284 Tz (minute ) Tj 51.428571 0 0 51.428571 0 2836.832536 Tm 25.297222 0 Td 45.730453 Tz (intervals ) Tj 2.683333 0 Td 51.851852 Tz (using ) Tj 1.711111 0 Td 58.333333 Tz (a ) Tj 0.525 0 Td 57.523148 Tz (Synergy2 ) Tj 2.936111 0 Td 55.416667 Tz (absorbance ) Tj 3.461111 0 Td 47.962963 Tz (plate ) Tj 1.613889 0 Td 50.771605 Tz (reader ) Tj 1.983333 0 Td 52.662037 Tz (\(BioTek, ) Tj 51.428571 0 0 51.428571 0 2795.841076 Tm 25.297222 0 Td 55.092593 Tz (Winooski, ) Tj 3.111111 0 Td 42.777778 Tz (Vt.\). ) Tj 1.516667 0 Td 49.537037 Tz (Results ) Tj 2.236111 0 Td 49.691358 Tz (are ) Tj 1.069444 0 Td 61.574074 Tz (shown ) Tj 1.983333 0 Td 46.990741 Tz (at ) Tj 0.719444 0 Td 48.611111 Tz (the ) Tj 1.011111 0 Td 59.41358 Tz (one ) Tj 1.205556 0 Td 56.712963 Tz (hour ) Tj 1.497222 0 Td 53.472222 Tz (time ) Tj 1.419444 0 Td 46.450617 Tz (point, ) Tj 51.428571 0 0 51.428571 0 2756.271523 Tm 25.277778 0 Td 65.625 Tz (when ) Tj 1.905556 0 Td 39.969136 Tz (all ) Tj 1.05 0 Td 54.768519 Tz (absorbance ) Tj 3.597222 0 Td 55.555556 Tz (changes ) Tj 2.663889 0 Td 50.231481 Tz (as ) Tj 0.913889 0 Td 58.333333 Tz (a ) Tj 0.680556 0 Td 49.826389 Tz (function ) Tj 2.722222 0 Td 58.333333 Tz (of ) Tj 0.894444 0 Td 55.092593 Tz (time ) Tj 1.652778 0 Td 58.333333 Tz (were ) Tj 51.428571 0 0 51.428571 0 2717.394872 Tm 25.297222 0 Td 42.12963 Tz (linear. ) Tj 2.158333 0 Td 55.092593 Tz (Readings ) Tj 2.994444 0 Td 58.333333 Tz (were ) Tj 1.730556 0 Td 54.444444 Tz (normalized ) Tj 3.597222 0 Td 45.37037 Tz (to ) Tj 0.875 0 Td 49.537037 Tz (vehicle ) Tj 2.372222 0 Td 49.537037 Tz (control ) Tj 2.391667 0 Td 46.018519 Tz (after ) Tj 40 0 0 40 0 2684 Tm 32.55 0 Td 62.5 Tz (subtraction ) Tj 4.475 0 Td 75 Tz (of ) Tj 1.125 0 Td 70.416667 Tz (absorbance ) Tj 4.575 0 Td 58.333333 Tz (in ) Tj 1.075 0 Td 63.888889 Tz (the ) Tj 1.475 0 Td 70.833333 Tz (absence ) Tj 3.325 0 Td 75 Tz (of ) Tj 1.125 0 Td 120.833333 Tz (CM ) Tj 1.8 0 Td 68.75 Tz (or ) Tj 1.125 0 Td 95.833333 Tz (CCM. ) Tj 40 0 0 40 0 2645 Tm 32.55 0 Td 72.916667 Tz (Data ) Tj 1.95 0 Td 65.277778 Tz (are ) Tj 1.4 0 Td 80 Tz (shown ) Tj 2.65 0 Td 64.583333 Tz (as ) Tj 1.025 0 Td 63.888889 Tz (the ) Tj 1.4 0 Td 76.851852 Tz (meantS.D. ) Tj 4.45 0 Td 72.916667 Tz (of ) Tj 0.975 0 Td 58.333333 Tz (at ) Tj 0.925 0 Td 57.5 Tz (least ) Tj 1.975 0 Td 61.666667 Tz (three ) Tj 2.1 0 Td 59.722222 Tz (wells. ) Tj 2.375 0 Td 66.666667 Tz (All ) Tj 51.428571 0 0 51.428571 0 2602.025516 Tm 25.297222 0 Td 53.619529 Tz (experiments ) Tj 3.811111 0 Td 58.333333 Tz (were ) Tj 1.633333 0 Td 51.446759 Tz (repeated ) Tj 2.683333 0 Td 53.796296 Tz (twice ) Tj 1.827778 0 Td 59.41358 Tz (and ) Tj 1.322222 0 Td 48.148148 Tz (representative ) Tj 4.316667 0 Td 44.444444 Tz (results ) Tj 40 0 0 40 0 2564 Tm 32.525 0 Td 63.888889 Tz (are ) Tj 1.4 0 Td 72.222222 Tz (shown. ) Tj 51.428571 0 0 51.428571 0 2516.71134 Tm 26.016667 0 Td 57.253086 Tz (Assays ) Tj 2.275 0 Td 59.143519 Tz (were ) Tj 1.594444 0 Td 56.532922 Tz (performed ) Tj 3.208333 0 Td 54.282407 Tz (with ) Tj 1.497222 0 Td 95.601852 Tz (CM ) Tj 1.361111 0 Td 50.231481 Tz (or ) Tj 0.797222 0 Td 89.660494 Tz (CCM ) Tj 1.808333 0 Td 57.523148 Tz (from ) Tj 1.652778 0 Td 69.675926 Tz (HEK293 ) Tj 51.428571 0 0 51.428571 0 2475.705463 Tm 25.297222 0 Td 44.074074 Tz (cells ) Tj 1.477778 0 Td 45.959596 Tz (transiently ) Tj 3.188889 0 Td 47.727273 Tz (transfected ) Tj 3.305556 0 Td 52.662037 Tz (with ) Tj 1.4 0 Td 69.675926 Tz (NPP6 ) Tj 1.808333 0 Td 58.333333 Tz (and ) Tj 1.186111 0 Td 55.092593 Tz (7 ) Tj 0.447222 0 Td 52.175926 Tz (expression ) Tj 3.227778 0 Td 59.143519 Tz (plas ) Tj 51.428571 0 0 51.428571 0 2432.759615 Tm 25.297222 0 Td 53.148148 Tz (mids, ) Tj 1.788889 0 Td 45.619658 Tz (respectively. ) Tj 3.772222 0 Td 69.675926 Tz (HEK293 ) Tj 2.702778 0 Td 44.074074 Tz (cells ) Tj 1.477778 0 Td 58.333333 Tz (were ) Tj 1.555556 0 Td 55.092593 Tz (seeded ) Tj 2.158333 0 Td 43.75 Tz (in ) Tj 0.719444 0 Td 54.768519 Tz (Dulbecco's ) Tj 51.428571 0 0 51.428571 0 2391.710493 Tm 25.297222 0 Td 53.877315 Tz (modified ) Tj 2.936111 0 Td 50.925926 Tz (Eagle's ) Tj 2.488889 0 Td 64.814815 Tz (medium ) Tj 2.683333 0 Td 76.157407 Tz (\(DMEM\) ) Tj 3.033333 0 Td 51.203704 Tz (containing ) Tj 3.461111 0 Td 69.135802 Tz (10% ) Tj 1.594444 0 Td 42.12963 Tz (fetal ) Tj 51.428571 0 0 51.428571 0 2352.215159 Tm 25.277778 0 Td 55.632716 Tz (bovine ) Tj 2.197222 0 Td 54.012346 Tz (serum, ) Tj 2.216667 0 Td 57.253086 Tz (100 ) Tj 1.244444 0 Td 61.574074 Tz (U/ml ) Tj 1.691667 0 Td 44.191919 Tz (penicillin, ) Tj 3.188889 0 Td 59.41358 Tz (100 ) Tj 1.283333 0 Td 55.092593 Tz (ug/ml ) Tj 1.866667 0 Td 52.932099 Tz (streptomycin ) Tj 51.428571 0 0 51.428571 0 2310.442211 Tm 25.316667 0 Td 52.932099 Tz (\(Hyclone, ) Tj 3.130556 0 Td 55.632716 Tz (Logan, ) Tj 2.275 0 Td 50.771605 Tz (Utah\), ) Tj 2.061111 0 Td 59.41358 Tz (and ) Tj 1.322222 0 Td 51.851852 Tz (2 ) Tj 0.622222 0 Td 97.222222 Tz (mM ) Tj 1.438889 0 Td 51.851852 Tz (L-glutamine. ) Tj 4.044444 0 Td 69.675926 Tz (HEK293 ) Tj 52.857143 0 0 52.857143 0 2266.410127 Tm 24.613514 0 Td 42.882883 Tz (cells ) Tj 1.456757 0 Td 58.333333 Tz (were ) Tj 1.589189 0 Td 59.90991 Tz (grown ) Tj 1.967568 0 Td 50.1001 Tz (overnight ) Tj 2.856757 0 Td 45.720721 Tz (at ) Tj 0.718919 0 Td 53.603604 Tz (37 ) Tj 1.172973 0 Td 52.027027 Tz (C. ) Tj 0.832432 0 Td 55.495495 Tz (under ) Tj 1.816216 0 Td 77.252252 Tz (5% ) Tj 1.097297 0 Td 68.318318 Tz (CO, ) Tj 1.475676 0 Td 42.567568 Tz (to ) Tj 0.718919 0 Td 71.471471 Tz (80% ) Tj 40 0 0 40 0 2231 Tm 32.525 0 Td 64.393939 Tz (confluence. ) Tj 4.7 0 Td 83.333333 Tz (The ) Tj 1.95 0 Td 56.666667 Tz (cells ) Tj 2.2 0 Td 76.041667 Tz (were ) Tj 2.275 0 Td 66.666667 Tz (then ) Tj 2.1 0 Td 62.121212 Tz (transfected ) Tj 4.55 0 Td 68.75 Tz (with ) Tj 2.1 0 Td 86.666667 Tz (human ) Tj 58.571429 0 0 58.571429 0 2184.484646 Tm 22.195122 0 Td 59.281843 Tz (NPP6ex ) Tj 2.885366 0 Td 48.373984 Tz (or ) Tj 0.853659 0 Td 58.04878 Tz (human ) Tj 2.031707 0 Td 58.333333 Tz (NPP7ex ) Tj 2.390244 0 Td 45.243902 Tz (expression ) Tj 3.039024 0 Td 46.595528 Tz (plasmids ) Tj 2.578049 0 Td 42.682927 Tz (in ) Tj 0.802439 0 Td 42.682927 Tz (the ) Tj 51.428571 0 0 51.428571 0 2143.961722 Tm 25.297222 0 Td 63.599537 Tz (pcDNA3.1 ) Tj 3.169444 0 Td 48.611111 Tz (\(+\) ) Tj 1.05 0 Td 63.014403 Tz (mammalian ) Tj 3.597222 0 Td 50.231481 Tz (vector ) Tj 1.944444 0 Td 46.990741 Tz (in ) Tj 0.738889 0 Td 49.691358 Tz (the ) Tj 1.05 0 Td 53.472222 Tz (presence ) Tj 2.722222 0 Td 55.092593 Tz (of ) Tj 0.777778 0 Td 50.636574 Tz (Polyfect ) Tj 51.428571 0 0 51.428571 0 2101.800766 Tm 25.297222 0 Td 50.501543 Tz (Transfection ) Tj 4.044444 0 Td 56.018519 Tz (Reagent ) Tj 2.683333 0 Td 53.292181 Tz (\(Hyclone, ) Tj 3.266667 0 Td 55.632716 Tz (Logan, ) Tj 2.372222 0 Td 49.691358 Tz (Utah\). ) Tj 2.177778 0 Td 52.932099 Tz (Six ) Tj 1.302778 0 Td 53.796296 Tz (hours ) Tj 51.428571 0 0 51.428571 0 2058.199516 Tm 25.297222 0 Td 45.37037 Tz (after ) Tj 1.477778 0 Td 46.367521 Tz (transfection, ) Tj 3.811111 0 Td 48.611111 Tz (the ) Tj 1.069444 0 Td 47.685185 Tz (culture ) Tj 2.177778 0 Td 65.354938 Tz (medium ) Tj 2.566667 0 Td 60.493827 Tz (was ) Tj 1.283333 0 Td 57.407407 Tz (changed ) Tj 2.547222 0 Td 48.611111 Tz (to ) Tj 0.758333 0 Td 59.62963 Tz (serum ) Tj 51.428571 0 0 51.428571 0 2018.188811 Tm 25.297222 0 Td 46.990741 Tz (free ) Tj 1.283333 0 Td 93.171296 Tz (DMEM ) Tj 2.313889 0 Td 51.527778 Tz (containing ) Tj 3.247222 0 Td 53.914141 Tz (L-glutamine ) Tj 3.655556 0 Td 59.41358 Tz (and ) Tj 1.147222 0 Td 44.722222 Tz (cells ) Tj 1.458333 0 Td 59.143519 Tz (were ) Tj 1.536111 0 Td 52.572016 Tz (incubated ) Tj 51.428571 0 0 51.428571 0 1976.646075 Tm 25.297222 0 Td 49.691358 Tz (for ) Tj 1.147222 0 Td 58.333333 Tz (48 ) Tj 0.991667 0 Td 49.691358 Tz (hours. ) Tj 2.158333 0 Td 54.372428 Tz (Expressed ) Tj 3.208333 0 Td 49.074074 Tz (protein ) Tj 2.372222 0 Td 60.493827 Tz (was ) Tj 1.4 0 Td 48.611111 Tz (collected ) Tj 2.916667 0 Td 64.166667 Tz (\(NPP6 ) Tj 2.197222 0 Td 60.493827 Tz (and ) Tj 51.428571 0 0 51.428571 0 1932.784689 Tm 25.277778 0 Td 65.462963 Tz (NPP7\) ) Tj 2.119444 0 Td 58.333333 Tz (and ) Tj 1.225 0 Td 51.58179 Tz (concentrated ) Tj 3.908333 0 Td 60.925926 Tz (-10x\(NPP7\) ) Tj 3.85 0 Td 53.148148 Tz (using ) Tj 1.788889 0 Td 56.712963 Tz (10 ) Tj 0.816667 0 Td 68.055556 Tz (kDa ) Tj 1.4 0 Td 65.895062 Tz (molecu ) Tj 51.428571 0 0 51.428571 0 1894.005202 Tm 25.297222 0 Td 44.290123 Tz (lar ) Tj 1.088889 0 Td 55.092593 Tz (weight ) Tj 2.294444 0 Td 50.771605 Tz (cutoff ) Tj 2.061111 0 Td 38.888889 Tz (filters ) Tj 1.963889 0 Td 47.727273 Tz (\(Millipore, ) Tj 3.538889 0 Td 49.016204 Tz (Beverly, ) Tj 2.683333 0 Td 54.012346 Tz (Mass.\) ) Tj 2.275 0 Td 45.37037 Tz (in ) Tj 0.855556 0 Td 59.953704 Tz (an ) Tj 51.428571 0 0 51.428571 0 1853.723589 Tm 25.297222 0 Td 64.814815 Tz (Amicon ) Tj 2.527778 0 Td 50.636574 Tz (pressure ) Tj 2.605556 0 Td 43.75 Tz (cell ) Tj 1.244444 0 Td 47.727273 Tz (\(Millipore, ) Tj 3.383333 0 Td 49.016204 Tz (Beverly, ) Tj 2.547222 0 Td 50.462963 Tz (Mass.\). ) Tj 40 0 0 40 0 1815 Tm 32.525 0 Td 64.583333 Tz (Test ) Tj 1.85 0 Td 63.690476 Tz (Results ) Tj 51.428571 0 0 51.428571 0 1767.145833 Tm 26.016667 0 Td 53.796296 Tz (Table ) Tj 1.847222 0 Td 38.888889 Tz (1 ) Tj 0.505556 0 Td 59.62963 Tz (shows ) Tj 2.002778 0 Td 48.611111 Tz (the ) Tj 1.088889 0 Td 44.444444 Tz (results ) Tj 2.061111 0 Td 58.333333 Tz (of ) Tj 0.797222 0 Td 77.777778 Tz (SAR ) Tj 1.594444 0 Td 49.494949 Tz (elaboration ) Tj 3.461111 0 Td 58.333333 Tz (and ) Tj 1.244444 0 Td 59.41358 Tz (optimi ) Tj 51.428571 0 0 51.428571 0 1727.480051 Tm 25.297222 0 Td 49.151235 Tz (zation ) Tj 2.158333 0 Td 59.953704 Tz (of ) Tj 1.030556 0 Td 50.231481 Tz (lead ) Tj 1.594444 0 Td 63.599537 Tz (compound ) Tj 3.5 0 Td 64.166667 Tz (H2L7905958 ) Tj 4.258333 0 Td 41.319444 Tz (\(1\). ) Tj 1.380556 0 Td 65.174897 Tz (Compounds ) Tj 52.857143 0 0 52.857143 0 1686.358282 Tm 24.632432 0 Td 56.306306 Tz (showing ) Tj 2.535135 0 Td 55.968468 Tz (improved ) Tj 2.875676 0 Td 78.828829 Tz (K ) Tj 0.813514 0 Td 48.348348 Tz (values ) Tj 1.910811 0 Td 52.815315 Tz (over ) Tj 1.381081 0 Td 50.45045 Tz (the ) Tj 1.040541 0 Td 49.662162 Tz (lead ) Tj 1.343243 0 Td 48.348348 Tz (are ) Tj 1.002703 0 Td 55.810811 Tz (emphasized ) Tj 3.518919 0 Td 47.297297 Tz (in ) Tj 52.857143 0 0 52.857143 0 1641.848606 Tm 24.594595 0 Td 53.603604 Tz (bold ) Tj 1.57027 0 Td 39.414414 Tz (italic ) Tj 1.740541 0 Td 42.252252 Tz (font. ) Tj 1.589189 0 Td 51.501502 Tz (Values ) Tj 2.194595 0 Td 60.540541 Tz (shown ) Tj 2.118919 0 Td 45.720721 Tz (in ) Tj 0.832432 0 Td 49.87715 Tz (parentheses ) Tj 3.632432 0 Td 44.774775 Tz (refer ) Tj 1.608108 0 Td 45.720721 Tz (to ) Tj 0.87027 0 Td 48.348348 Tz (the ) Tj 51.428571 0 0 51.428571 0 1599.490566 Tm 25.297222 0 Td 64.00463 Tz (compound ) Tj 3.227778 0 Td 58.333333 Tz (numbers ) Tj 2.586111 0 Td 51.446759 Tz (\(FIG.5\). ) Tj 2.663889 0 Td 48.070988 Tz (Errors ) Tj 1.886111 0 Td 59.62963 Tz (where ) Tj 1.905556 0 Td 49.331276 Tz (indicated ) Tj 2.761111 0 Td 50.771605 Tz (are ) Tj 1.030556 0 Td 58.333333 Tz (stan ) Tj 51.428571 0 0 51.428571 0 1560.74 Tm 25.297222 0 Td 54.282407 Tz (dard ) Tj 1.594444 0 Td 48.935185 Tz (deviations ) Tj 3.266667 0 Td 55.092593 Tz (of ) Tj 0.855556 0 Td 45.37037 Tz (at ) Tj 0.816667 0 Td 44.722222 Tz (least ) Tj 1.594444 0 Td 49.907407 Tz (three ) Tj 1.769444 0 Td 53.914141 Tz (independent ) Tj 3.830556 0 Td 51.58179 Tz (experiments. ) Tj 51.428571 0 0 51.428571 0 1517.377312 Tm 25.316667 0 Td 50.231481 Tz (ICso ) Tj 1.497222 0 Td 50.231481 Tz (values ) Tj 2.022222 0 Td 51.388889 Tz (lacking ) Tj 2.372222 0 Td 51.041667 Tz (standard ) Tj 2.663889 0 Td 49.259259 Tz (deviations ) Tj 3.15 0 Td 50.771605 Tz (are ) Tj 1.088889 0 Td 52.662037 Tz (averages ) Tj 2.780556 0 Td 56.712963 Tz (of ) Tj 0.777778 0 Td 59.41358 Tz (two ) Tj 51.428571 0 0 51.428571 0 1477.560976 Tm 25.297222 0 Td 53.914141 Tz (independent ) Tj 3.733333 0 Td 53.619529 Tz (experiments ) Tj 3.752778 0 Td 45.37037 Tz (that ) Tj 1.283333 0 Td 58.333333 Tz (were ) Tj 1.594444 0 Td 44.560185 Tz (less ) Tj 1.263889 0 Td 51.851852 Tz (than ) Tj 1.438889 0 Td 81.018519 Tz (3% ) Tj 1.147222 0 Td 46.090535 Tz (different ) Tj 2.683333 0 Td 48.611111 Tz (in ) Tj 40 0 0 40 0 1440 Tm 32.525 0 Td 61.111111 Tz (value. ) Tj 38.571429 0 0 38.571429 0 1369 Tm 40.418519 0 Td 101.111111 Tz (TABLE ) Tj 3.37037 0 Td 23.765432 Tz (1. ) Tj 85.714286 0 0 85.714286 0 1157 Tm 17.22 0 Td 35 Tz (B ) Tj 37.142857 0 0 37.142857 0 1134 Tm 40.330769 0 Td 170.512821 Tz (2 ) Tj 35.714286 0 0 35.714286 0 1109 Tm 44.492 0 Td 107.333333 Tz (N ) Tj 9.716 0 Td 70 Tz (R5 ) Tj 31.428571 0 0 31.428571 0 1070.846154 Tm 52.436364 0 Td 100.757576 Tz (C ) Tj 5.536364 0 Td 106.060606 Tz (H ) Tj 90 0 0 90 0 990.72449 Tm 18.933333 0 Td 124.074074 Tz (N ) Tj 3.855556 0 Td 28.703704 Tz (R4 ) Tj 31.428571 0 0 31.428571 0 942 Tm 56.190909 0 Td 74.242424 Tz (S ) Tj 40 0 0 40 0 909 Tm 45.375 0 Td 60.416667 Tz (R1 ) Tj 5.9 0 Td 62.5 Tz (R3 ) Tj 40 0 0 40 0 842 Tm 48.4 0 Td 62.5 Tz (R2 ) Tj 38.571429 0 0 38.571429 0 769.925373 Tm 40.055556 0 Td 103.703704 Tz (% ) Tj 0.881481 0 Td 59.41358 Tz (Response ) Tj 37.428571 0 0 37.428571 0 735.087558 Tm 41.78626 0 Td 48.982188 Tz (at ) Tj 0.801527 0 Td 60.114504 Tz (10 ) Tj 1.335878 0 Td 115.776081 Tz (M ) Tj 7.454198 0 Td 51.653944 Tz (Inhibition ) Tj 5.477099 0 Td 57.888041 Tz (K. ) Tj 38.285714 0 0 38.285714 0 700.154255 Tm 41.268657 0 Td 53.689884 Tz (\(FS-3\) ) Tj 3.996269 0 Td 54.415423 Tz (ICso ) Tj 1.514925 0 Td 64.210199 Tz (\(IM\) ) Tj 3.186567 0 Td 65.298507 Tz (Mechanism ) Tj 5.197761 0 Td 63.121891 Tz (\(IM\) ) Tj 31.632653 0 0 31.632653 0 642.376623 Tm 46.470968 0 Td 56.200717 Tz (\(1\) ) Tj 3.003226 0 Td 63.225806 Tz (O.O ) Tj 2.086452 0 Td 64.982079 Tz (4.O ) Tj 3.509032 0 Td 50.053763 Tz (1...6+ ) Tj 2.054839 0 Td 64.982079 Tz (0.4 ) Tj 4.299355 0 Td 79.032258 Tz (Mixed ) Tj 5.500645 0 Td 59.713262 Tz (1.6 ) Tj 32.857143 0 0 32.857143 0 575.330166 Tm 44.526087 0 Td 59.601449 Tz (\(11\) ) Tj 3.104348 0 Td 88.768116 Tz (O3 ) Tj 1.430435 0 Td 45.652174 Tz (+ ) Tj 0.63913 0 Td 59.178744 Tz (0.6 ) Tj 3.256522 0 Td 86.231884 Tz (O.90.3 ) Tj 5.143478 0 Td 65.942029 Tz (Competitive ) Tj 6.269565 0 Td 63.405797 Tz (O.O3 ) Tj 32.285714 0 0 32.285714 0 481.037543 Tm 45.314159 0 Td 60.656342 Tz (\(20\) ) Tj 3.159292 0 Td 107.374631 Tz (5.404 ) Tj 6.752212 0 Td 56.784661 Tz (1.7 ) Tj 4.955752 0 Td 77.433628 Tz (Mixed ) Tj 5.389381 0 Td 58.505408 Tz (1.7 ) Tj 35 0 0 35 0 413.655462 Tm 41.8 0 Td 55.952381 Tz (\(29\) ) Tj 2.942857 0 Td 55.555556 Tz (8.6 ) Tj 1.885714 0 Td 57.142857 Tz (O.9 ) Tj 4.314286 0 Td 52.380952 Tz (1.6 ) Tj 3.171429 0 Td 63.369963 Tz (Uncompetitive ) Tj 6.371429 0 Td 52.380952 Tz (1.5 ) Tj 31.428571 0 0 31.428571 0 318.081433 Tm 46.55 0 Td 62.310606 Tz (\(14\) ) Tj 3.245455 0 Td 63.636364 Tz (9.7 ) Tj 2.163636 0 Td 61.868687 Tz (O.9 ) Tj 3.404545 0 Td 61.868687 Tz (2.5 ) Tj 1.495455 0 Td 47.727273 Tz (+ ) Tj 0.668182 0 Td 61.868687 Tz (0.2 ) Tj 4.295455 0 Td 79.545455 Tz (Mixed ) Tj 5.472727 0 Td 61.868687 Tz (2.5 ) Tj 35.555556 0 0 35.555556 0 246.138425 Tm 41.34375 0 Td 50 Tz (\(7\) ) Tj 2.278125 0 Td 58.59375 Tz (28.6 ) Tj 1.6875 0 Td 60.9375 Tz (+ ) Tj 0.61875 0 Td 54.6875 Tz (2.0 ) Tj 2.64375 0 Td 55.078125 Tz (12.1 ) Tj 1.659375 0 Td 56.25 Tz (+ ) Tj 0.590625 0 Td 57.8125 Tz (2.4 ) Tj 2.86875 0 Td 60.9375 Tz (Competitive ) Tj 5.79375 0 Td 78.125 Tz (O43 ) Tj 1.428571 0 0 1.428571 0 1330 Tm 884.8 0 Td 116.666667 Tz ( ) Tj ET Q endstream endobj 298 0 obj << /Length 1 >> stream q endstream endobj 299 0 obj << /Length 26973 >> stream Q q 0.24 0 0 0.24 0 0 cm BT /F1 1 Tf 3 Tr 62.857143 0 0 62.857143 0 3023 Tm 17.325 0 Td 83.522727 Tz (US ) Tj 1.240909 0 Td 57.154882 Tz (8,497,371 ) Tj 3.388636 0 Td 74.242424 Tz (B2 ) Tj 52.857143 0 0 52.857143 0 2968 Tm 14.208108 0 Td 75.675676 Tz (23 ) Tj 40 0 0 40 0 2913 Tm 18.55 0 Td 97.5 Tz (TABLE ) Tj 3.225 0 Td 67.424242 Tz (1-continued ) Tj 51.428571 0 0 51.428571 0 2969 Tm 33.541667 0 Td 79.398148 Tz (24 ) Tj 31.428571 0 0 31.428571 0 2786 Tm 14.190909 0 Td 106.060606 Tz (HOOC ) Tj 31.428571 0 0 31.428571 0 2753 Tm 25.263636 0 Td 121.969697 Tz (N ) Tj 114.285714 0 0 114.285714 0 2670 Tm 6.5625 0 Td 48.125 Tz (als ) Tj 37.142857 0 0 37.142857 0 2678 Tm 20.676923 0 Td 139.102564 Tz (2 ) Tj 83.571429 0 0 83.571429 0 2620.15748 Tm 10.577778 0 Td 96.723647 Tz (1\) ) Tj 3.769231 0 Td 29.91453 Tz (R5 ) Tj 75.714286 0 0 75.714286 0 2562.822785 Tm 11.358491 0 Td 123.820755 Tz (N-N- ) Tj 6.260377 0 Td 26.415094 Tz (4 ) Tj 85.714286 0 0 85.714286 0 2525.380952 Tm 11.293333 0 Td 130.277778 Tz (N ) Tj 4.071667 0 Td 33.055556 Tz (R ) Tj 31.428571 0 0 31.428571 0 2486 Tm 32.740909 0 Td 74.242424 Tz (S ) Tj 38.571429 0 0 38.571429 0 2453 Tm 27.974074 0 Td 60.493827 Tz (RI ) Tj 6.118519 0 Td 64.814815 Tz (R3 ) Tj 40 0 0 40 0 2386 Tm 29.975 0 Td 62.5 Tz (R2 ) Tj 38.571429 0 0 38.571429 0 2312.925373 Tm 20.974074 0 Td 103.703704 Tz (% ) Tj 0.855556 0 Td 59.41358 Tz (Response ) Tj 37.142857 0 0 37.142857 0 2278.311321 Tm 22.265385 0 Td 49.358974 Tz (at ) Tj 0.807692 0 Td 60.576923 Tz (10 ) Tj 1.346154 0 Td 116.666667 Tz (M ) Tj 7.511538 0 Td 52.5 Tz (Inhibition ) Tj 5.546154 0 Td 89.74359 Tz (K ) Tj 39.365079 0 0 39.365079 0 2243.611475 Tm 10.94879 0 Td 49.042339 Tz (Substitution ) Tj 3.734274 0 Td 61.391129 Tz (on ) Tj 0.990726 0 Td 80.443548 Tz (D ) Tj 0.685887 0 Td 48.689516 Tz (ring ) Tj 5.055242 0 Td 52.217742 Tz (\(FS-3\) ) Tj 3.886694 0 Td 52.923387 Tz (ICso ) Tj 1.473387 0 Td 49.959677 Tz (\(LIM\) ) Tj 3.099194 0 Td 63.978495 Tz (Mechanism ) Tj 5.080645 0 Td 61.391129 Tz (\(IM\) ) Tj 38.412698 0 0 38.412698 0 2150.330645 Tm 10.673554 0 Td 59.659091 Tz (Dimethyl ) Tj 3.071901 0 Td 81.570248 Tz (\(R,R\) ) Tj 5.154545 0 Td 50.981405 Tz (\(22\) ) Tj 2.316942 0 Td 54.235537 Tz (30.4 ) Tj 1.509917 0 Td 60.743802 Tz (+ ) Tj 0.59876 0 Td 49.173554 Tz (1.3 ) Tj 3.852893 0 Td 52.066116 Tz (9.0 ) Tj 4.217355 0 Td 65.082645 Tz (Mixed ) Tj 4.711983 0 Td 52.066116 Tz (9.0 ) Tj 37.285714 0 0 37.285714 0 2117.923567 Tm 11.559387 0 Td 59.227331 Tz (Iodo ) Tj 1.662835 0 Td 60.344828 Tz (\(para-R\) ) Tj 6.436782 0 Td 47.679864 Tz (\(3\) ) Tj 2.172414 0 Td 55.87484 Tz (32.7 ) Tj 1.609195 0 Td 58.109834 Tz (+ ) Tj 0.616858 0 Td 49.16986 Tz (1.3 ) Tj 2.842912 0 Td 53.639847 Tz (5.6 ) Tj 1.823755 0 Td 52.149851 Tz (0.2 ) Tj 3.62069 0 Td 67.049808 Tz (Mixed ) Tj 4.854406 0 Td 53.639847 Tz (S.6 ) Tj 37.922078 0 0 37.922078 0 2045.368567 Tm 9.334932 0 Td 54.549423 Tz (Ditrifluoromethyl ) Tj 5.775 0 Td 82.625571 Tz (\(R,R\) ) Tj 4.034589 0 Td 51.640982 Tz (\(18\) ) Tj 2.346918 0 Td 51.640982 Tz (34.1 ) Tj 1.529452 0 Td 61.52968 Tz (+ ) Tj 0.580137 0 Td 52.739726 Tz (3.0 ) Tj 2.821575 0 Td 83.504566 Tz (44 ) Tj 1.239384 0 Td 21.974886 Tz (- ) Tj 0.606507 0 Td 48.344749 Tz (1.5 ) Tj 2.636986 0 Td 57.534247 Tz (Competitive ) Tj 5.669521 0 Td 73.249619 Tz (O16 ) Tj 39.68254 0 0 39.68254 0 1951.103448 Tm 8.8956 0 Td 54.04 Tz (Trifluoromethyl ) Tj 5.04 0 Td 60.375 Tz (\(para-R\) ) Tj 4.3596 0 Td 49.35 Tz (\(31\) ) Tj 2.2428 0 Td 51.45 Tz (36.2 ) Tj 1.4616 0 Td 58.8 Tz (+ ) Tj 0.5544 0 Td 50.4 Tz (0.9 ) Tj 3.8052 0 Td 46.2 Tz (1.5 ) Tj 2.7972 0 Td 56.215385 Tz (Uncompetitive ) Tj 5.8464 0 Td 49 Tz (1.4 ) Tj 37.142857 0 0 37.142857 0 1859.208333 Tm 11.226923 0 Td 63.782051 Tz (Fluoro\(meta-R\) ) Tj 8.319231 0 Td 52.724359 Tz (\(25\) ) Tj 2.342308 0 Td 56.089744 Tz (40.5 ) Tj 1.615385 0 Td 62.820513 Tz (+ ) Tj 0.619231 0 Td 52.350427 Tz (1.0 ) Tj 2.530769 0 Td 52.724359 Tz (16.1 ) Tj 1.588462 0 Td 22.435897 Tz (- ) Tj 0.565385 0 Td 52.350427 Tz (4.5 ) Tj 38.928571 0 0 38.928571 0 1827.753333 Tm 10.326606 0 Td 64.220183 Tz (Methoxy ) Tj 2.902752 0 Td 61.544343 Tz (\(meta-R\) ) Tj 5.420183 0 Td 50.30581 Tz (\(19\) ) Tj 2.234862 0 Td 54.587156 Tz (40.9 ) Tj 1.541284 0 Td 59.938838 Tz (+ ) Tj 0.590826 0 Td 48.521916 Tz (1.3 ) Tj 2.414679 0 Td 52.446483 Tz (17.7 ) Tj 2.055046 0 Td 49.949032 Tz (O.3 ) Tj 36.623377 0 0 36.623377 0 1795.318919 Tm 11.249645 0 Td 63.711584 Tz (Methyl ) Tj 2.539362 0 Td 64.849291 Tz (\(meta-R\) ) Tj 6.034397 0 Td 53.472222 Tz (\(13\) ) Tj 2.375532 0 Td 58.02305 Tz (41.9 ) Tj 1.638298 0 Td 63.711584 Tz (+ ) Tj 0.600709 0 Td 54.609929 Tz (0.8 ) Tj 2.593972 0 Td 54.609929 Tz (13.5 ) Tj 1.610993 0 Td 22.754137 Tz (- ) Tj 0.628014 0 Td 50.059102 Tz (1.3 ) Tj 3.658865 0 Td 68.262411 Tz (Mixed ) Tj 4.587234 0 Td 54.609929 Tz (13.5 ) Tj 38.412698 0 0 38.412698 0 1761.517578 Tm 10.855785 0 Td 58.57438 Tz (Chloro ) Tj 2.316942 0 Td 59.116736 Tz (\(para-R\) ) Tj 5.727273 0 Td 50.981405 Tz (\(28\) ) Tj 2.264876 0 Td 56.404959 Tz (42.4 ) Tj 1.561983 0 Td 60.743802 Tz (+ ) Tj 0.572727 0 Td 52.066116 Tz (0.9 ) Tj 3.540496 0 Td 53.150826 Tz (10.7 ) Tj 4.555785 0 Td 65.082645 Tz (Mixed ) Tj 4.373554 0 Td 53.150826 Tz (10.7 ) Tj 40.612245 0 0 40.612245 0 1727.777778 Tm 10.341709 0 Td 51.982133 Tz (Fluoro ) Tj 2.092965 0 Td 55.40201 Tz (\(para-R\) ) Tj 5.441709 0 Td 48.220268 Tz (\(23\) ) Tj 2.142211 0 Td 52.324121 Tz (48.9 ) Tj 1.477387 0 Td 57.453936 Tz (+ ) Tj 0.566332 0 Td 45.142379 Tz (1.1 ) Tj 3.324121 0 Td 50.272194 Tz (17.7 ) Tj 37.936508 0 0 37.936508 0 1696.346247 Tm 10.96569 0 Td 61.506276 Tz (Methyl ) Tj 2.398745 0 Td 59.858787 Tz (\(para-R\) ) Tj 5.772803 0 Td 51.621339 Tz (\(27\) ) Tj 2.293305 0 Td 56.014644 Tz (49.9 ) Tj 1.58159 0 Td 61.506276 Tz (+ ) Tj 0.606276 0 Td 49.790795 Tz (1.5 ) Tj 2.477824 0 Td 51.621339 Tz (16.1 ) Tj 1.55523 0 Td 52.719665 Tz (+ ) Tj 0.553556 0 Td 65.899582 Tz (4 ) Tj 40 0 0 40 0 1661.179931 Tm 10.825 0 Td 54.6875 Tz (O-methyl ) Tj 2.8 0 Td 46.666667 Tz (ester ) Tj 4.7 0 Td 44.444444 Tz (\(5\) ) Tj 2.025 0 Td 52.083333 Tz (51.2 ) Tj 1.5 0 Td 54.166667 Tz (+ ) Tj 0.575 0 Td 45.833333 Tz (1.3 ) Tj 44.489796 0 0 44.489796 0 1626.12963 Tm 8.65367 0 Td 47.867822 Tz (Trimethyl ) Tj 2.764679 0 Td 44.954128 Tz (\(R', ) Tj 1.236239 0 Td 78.669725 Tz (R,R\) ) Tj 3.821101 0 Td 41.207951 Tz (\(8\) ) Tj 1.820642 0 Td 46.827217 Tz (53.5 ) Tj 1.326147 0 Td 52.446483 Tz (+ ) Tj 0.53945 0 Td 42.456677 Tz (1.6 ) Tj 38 0 0 38 0 1591.625767 Tm 13.394737 0 Td 74.561404 Tz (H ) Tj 5.710526 0 Td 51.535088 Tz (\(16\) ) Tj 2.342105 0 Td 54.824561 Tz (56.4 ) Tj 1.526316 0 Td 61.403509 Tz (+ ) Tj 0.605263 0 Td 51.169591 Tz (1.0 ) Tj 40 0 0 40 0 1562.153846 Tm 9.3 0 Td 54.545455 Tz (4-dimethylaminonapthyl ) Tj 9.025 0 Td 44.444444 Tz (\(2\) ) Tj 2.025 0 Td 52.083333 Tz (59.9 ) Tj 1.5 0 Td 54.166667 Tz (+ ) Tj 0.575 0 Td 45.833333 Tz (1.5 ) Tj 42.44898 0 0 42.44898 0 1525 Tm 9.328846 0 Td 49.256993 Tz (Thiadiazole ) Tj 3.415865 0 Td 46.133814 Tz (\(R', ) Tj 1.319231 0 Td 76.5625 Tz (R\) ) Tj 3.038942 0 Td 46.133814 Tz (\(10\) ) Tj 2.096635 0 Td 48.096955 Tz (63.2 ) Tj 1.366346 0 Td 54.967949 Tz (+ ) Tj 0.518269 0 Td 47.115385 Tz (2.8 ) Tj 47.142857 0 0 47.142857 0 1496.065401 Tm 7.254545 0 Td 45.763187 Tz (Sulfonylmorpholine ) Tj 5.090909 0 Td 48.611111 Tz (\(para-R\) ) Tj 3.181818 0 Td 40.06734 Tz (\(6\) ) Tj 1.739394 0 Td 41.540404 Tz (64.1 ) Tj 1.272727 0 Td 45.959596 Tz (+ ) Tj 0.424242 0 Td 43.602694 Tz (2.8 ) Tj 41.904762 0 0 41.904762 0 1458 Tm 10.142045 0 Td 52.698864 Tz (Iodo ) Tj 1.479545 0 Td 47.727273 Tz (\(ortho-R'\) ) Tj 5.703409 0 Td 46.732955 Tz (\(26\) ) Tj 2.123864 0 Td 49.715909 Tz (68.4 ) Tj 1.384091 0 Td 55.681818 Tz (+ ) Tj 0.548864 0 Td 45.075758 Tz (1.3 ) Tj 42.285714 0 0 42.285714 0 1429.236311 Tm 9.625 0 Td 50.253378 Tz (Pyrazole ) Tj 2.601351 0 Td 53.209459 Tz (\(para-R\) ) Tj 5.108108 0 Td 42.042042 Tz (\(9\) ) Tj 1.915541 0 Td 57.545045 Tz (68.6+ ) Tj 1.962838 0 Td 42.042042 Tz (1.1 ) Tj 42.44898 0 0 42.44898 0 1392 Tm 9.729327 0 Td 50.550881 Tz (Dichloro ) Tj 2.638462 0 Td 45.152244 Tz (\(R', ) Tj 1.319231 0 Td 74.599359 Tz (R\) ) Tj 3.415865 0 Td 46.133814 Tz (\(15\) ) Tj 2.096635 0 Td 47.115385 Tz (72.3 ) Tj 1.366346 0 Td 54.967949 Tz (+ ) Tj 0.518269 0 Td 48.424145 Tz (0.4 ) Tj 40 0 0 40 0 1360.916996 Tm 11.4 0 Td 51.25 Tz (p-carboxyl ) Tj 6.925 0 Td 44.444444 Tz (\(4\) ) Tj 2.025 0 Td 52.083333 Tz (72.7 ) Tj 1.5 0 Td 54.166667 Tz (+ ) Tj 0.55 0 Td 48.611111 Tz (2.2 ) Tj 41.904762 0 0 41.904762 0 1325 Tm 9.855682 0 Td 50.378788 Tz (Fluoro ) Tj 2.028409 0 Td 48.125 Tz (\(ortho-R'\) ) Tj 5.440909 0 Td 46.732955 Tz (\(30\) ) Tj 2.123864 0 Td 47.727273 Tz (77.3 ) Tj 1.384091 0 Td 55.681818 Tz (+ ) Tj 0.548864 0 Td 46.401515 Tz (1.6 ) Tj 41.904762 0 0 41.904762 0 1296.168975 Tm 9.664773 0 Td 60.227273 Tz (Methoxy ) Tj 2.696591 0 Td 54.190341 Tz (\(para-R\) ) Tj 4.963636 0 Td 46.732955 Tz (\(24\) ) Tj 2.123864 0 Td 48.721591 Tz (79.7 ) Tj 1.384091 0 Td 55.681818 Tz (+ ) Tj 0.525 0 Td 47.727273 Tz (0.9 ) Tj 42.380952 0 0 42.380952 0 1258 Tm 9.721348 0 Td 52.434457 Tz (Chloro ) Tj 2.1 0 Td 46.797753 Tz (\(ortho-R'\) ) Tj 5.308989 0 Td 46.207865 Tz (\(17\) ) Tj 2.1 0 Td 47.191011 Tz (83.5 ) Tj 1.368539 0 Td 55.05618 Tz (+ ) Tj 0.519101 0 Td 47.191011 Tz (8.2 ) Tj 42.857143 0 0 42.857143 0 1226.952632 Tm 9.31 0 Td 58.888889 Tz (Methoxy ) Tj 2.66 0 Td 46.277778 Tz (\(ortho-R'\) ) Tj 4.97 0 Td 45.694444 Tz (\(21\) ) Tj 2.053333 0 Td 56.777778 Tz (97.6+ ) Tj 1.913333 0 Td 45.37037 Tz (1.8 ) Tj 41.904762 0 0 41.904762 0 1194.775862 Tm 8.590909 0 Td 48.787879 Tz (Trifluoromethyl ) Tj 4.581818 0 Td 47.727273 Tz (\(ortho-R"\) ) Tj 4.152273 0 Td 46.732955 Tz (\(12\) ) Tj 1.765909 0 Td 50.909091 Tz (100.8 ) Tj 1.742045 0 Td 55.681818 Tz (+ ) Tj 0.548864 0 Td 46.401515 Tz (1.9 ) Tj 51.428571 0 0 51.428571 0 1053.454545 Tm 7.097222 0 Td 53.148148 Tz (Table ) Tj 1.711111 0 Td 58.333333 Tz (2 ) Tj 0.525 0 Td 57.361111 Tz (summarizes ) Tj 3.577778 0 Td 59.41358 Tz (two ) Tj 1.225 0 Td 52.572016 Tz (important ) Tj 2.975 0 Td 48.611111 Tz (trends ) Tj 1.925 0 Td 44.560185 Tz (that ) Tj 1.186111 0 Td 71.296296 Tz (we ) Tj 0.991667 0 Td 55.092593 Tz (observed ) Tj 51.428571 0 0 51.428571 0 1017.45322 Tm 6.338889 0 Td 54.282407 Tz (with ) Tj 1.477778 0 Td 51.203704 Tz (these ) Tj 1.711111 0 Td 49.826389 Tz (analogs, ) Tj 2.605556 0 Td 53.796296 Tz (being ) Tj 1.769444 0 Td 51.851852 Tz (the ) Tj 1.127778 0 Td 48.070988 Tz (single ) Tj 1.925 0 Td 55.092593 Tz (dose ) Tj 1.516667 0 Td 53.06713 Tz (response ) Tj 2.722222 0 Td 62.5 Tz (compari ) Tj 51.428571 0 0 51.428571 0 974.689567 Tm 6.377778 0 Td 54.012346 Tz (son ) Tj 1.244444 0 Td 59.953704 Tz (by ) Tj 0.991667 0 Td 53.06713 Tz (aromatic ) Tj 2.838889 0 Td 47.727273 Tz (Substituent ) Tj 3.402778 0 Td 58.333333 Tz (and ) Tj 1.302778 0 Td 46.450617 Tz (position. ) Tj 2.780556 0 Td 52.932099 Tz (Values ) Tj 2.197222 0 Td 61.574074 Tz (shown ) Tj 2.138889 0 Td 48.611111 Tz (in ) Tj 51.428571 0 0 51.428571 0 936.453836 Tm 6.358333 0 Td 51.262626 Tz (parentheses ) Tj 3.597222 0 Td 45.37037 Tz (refer ) Tj 1.536111 0 Td 45.37037 Tz (to ) Tj 0.758333 0 Td 49.691358 Tz (the ) Tj 1.069444 0 Td 64.00463 Tz (compound ) Tj 3.266667 0 Td 58.796296 Tz (numbers ) Tj 2.663889 0 Td 50.231481 Tz (as ) Tj 0.797222 0 Td 45.37037 Tz (in ) Tj 0.719444 0 Td 53.796296 Tz (Table ) Tj 1.847222 0 Td 38.888889 Tz (1. ) Tj 38.571429 0 0 38.571429 0 854 Tm 18.251852 0 Td 101.111111 Tz (TABLE ) Tj 3.266667 0 Td 77.777778 Tz (2 ) Tj 38.571429 0 0 38.571429 0 787 Tm 14.544444 0 Td 74.176955 Tz (Meta-R ) Tj 6.144444 0 Td 67.695473 Tz (Para-R ) Tj 6.196296 0 Td 57.901235 Tz (Ortho ) Tj 1.944444 0 Td 38.888889 Tz (- ) Tj 0.440741 0 Td 62.654321 Tz (R' ) Tj 39.340659 0 0 39.340659 0 720.556962 Tm 8.312011 0 Td 46.60149 Tz (Tri- ) Tj 5.515922 0 Td 49.425822 Tz (0.3 ) Tj 1.169274 0 Td 55.074488 Tz (+ ) Tj 0.559218 0 Td 49.425822 Tz (0.6 ) Tj 1.296369 0 Td 49.778864 Tz (\(11\) ) Tj 2.51648 0 Td 54.015363 Tz (36.2 ) Tj 1.52514 0 Td 55.074488 Tz (+ ) Tj 0.584637 0 Td 48.013656 Tz (0.9 ) Tj 1.296369 0 Td 48.719739 Tz (\(31\) ) Tj 2.948603 0 Td 53.379888 Tz (100.8 ) Tj 1.830168 0 Td 55.074488 Tz (+ ) Tj 0.610056 0 Td 46.60149 Tz (1.9 ) Tj 1.245531 0 Td 49.778864 Tz (\(12\) ) Tj 40 0 0 40 0 693 Tm 8.175 0 Td 52.083333 Tz (fluoromethyl ) Tj 39.340659 0 0 39.340659 0 654.698901 Tm 8.312011 0 Td 56.133613 Tz (Iodo ) Tj 5.541341 0 Td 49.425822 Tz (8.6 ) Tj 1.143855 0 Td 55.074488 Tz (+ ) Tj 0.559218 0 Td 49.425822 Tz (0.9 ) Tj 1.296369 0 Td 49.778864 Tz (\(29\) ) Tj 2.51648 0 Td 54.015363 Tz (32.7 ) Tj 1.52514 0 Td 55.074488 Tz (+ ) Tj 0.610056 0 Td 45.189323 Tz (1.3 ) Tj 1.27095 0 Td 45.189323 Tz (\(3\) ) Tj 3.27905 0 Td 54.015363 Tz (68.4 ) Tj 1.474302 0 Td 59.310987 Tz (+ ) Tj 0.610056 0 Td 46.60149 Tz (1.3 ) Tj 1.296369 0 Td 48.719739 Tz (\(26\) ) Tj 39.340659 0 0 39.340659 0 620.956175 Tm 8.312011 0 Td 56.486654 Tz (Chloro ) Tj 5.515922 0 Td 50.837989 Tz (9.7 ) Tj 1.169274 0 Td 55.074488 Tz (+ ) Tj 0.559218 0 Td 49.425822 Tz (0.9 ) Tj 1.296369 0 Td 49.778864 Tz (\(14\) ) Tj 2.465642 0 Td 57.192737 Tz (42.4 ) Tj 1.575978 0 Td 55.074488 Tz (+ ) Tj 0.584637 0 Td 48.013656 Tz (0.9 ) Tj 1.296369 0 Td 48.719739 Tz (\(28\) ) Tj 3.27905 0 Td 51.897114 Tz (83.5 ) Tj 1.474302 0 Td 59.310987 Tz (+ ) Tj 0.584637 0 Td 49.425822 Tz (8.2 ) Tj 1.321788 0 Td 48.719739 Tz (\(17\) ) Tj 39.340659 0 0 39.340659 0 587.90411 Tm 8.312011 0 Td 54.368405 Tz (Fluoro ) Tj 5.109218 0 Td 54.015363 Tz (40.5 ) Tj 1.575978 0 Td 55.074488 Tz (+ ) Tj 0.584637 0 Td 48.013656 Tz (1.0 ) Tj 1.27095 0 Td 49.778864 Tz (\(25\) ) Tj 2.491061 0 Td 55.074488 Tz (48.9 ) Tj 1.52514 0 Td 59.310987 Tz (+ ) Tj 0.610056 0 Td 45.189323 Tz (1.1 ) Tj 1.27095 0 Td 49.778864 Tz (\(23\) ) Tj 3.27905 0 Td 52.956238 Tz (77.3 ) Tj 1.499721 0 Td 59.310987 Tz (+ ) Tj 0.610056 0 Td 48.013656 Tz (1.6 ) Tj 1.296369 0 Td 48.719739 Tz (\(30\) ) Tj 40 0 0 40 0 555.156364 Tm 8.175 0 Td 63.095238 Tz (Methoxy ) Tj 5.025 0 Td 54.166667 Tz (40.9 ) Tj 1.55 0 Td 54.166667 Tz (+ ) Tj 0.575 0 Td 45.833333 Tz (1.3 ) Tj 1.25 0 Td 48.958333 Tz (\(19\) ) Tj 2.5 0 Td 52.083333 Tz (79.7 ) Tj 1.45 0 Td 58.333333 Tz (+ ) Tj 0.575 0 Td 48.611111 Tz (0.9 ) Tj 1.275 0 Td 48.958333 Tz (\(24\) ) Tj 3.225 0 Td 60.833333 Tz (97.6+ ) Tj 2.075 0 Td 47.222222 Tz (1.8 ) Tj 1.275 0 Td 47.916667 Tz (\(21\) ) Tj 51.428571 0 0 51.428571 0 454.419689 Tm 7.097222 0 Td 53.796296 Tz (Thus, ) Tj 1.808333 0 Td 32.407407 Tz (it ) Tj 0.525 0 Td 56.17284 Tz (can ) Tj 1.186111 0 Td 58.333333 Tz (be ) Tj 0.836111 0 Td 52.662037 Tz (seen ) Tj 1.458333 0 Td 46.180556 Tz (that ) Tj 1.244444 0 Td 46.990741 Tz (inhibition ) Tj 2.994444 0 Td 55.497685 Tz (improves ) Tj 2.858333 0 Td 57.523148 Tz (from ) Tj 1.555556 0 Td 50.555556 Tz (ortho ) Tj 1.711111 0 Td 45.37037 Tz (to ) Tj 51.428571 0 0 51.428571 0 417.393939 Tm 6.358333 0 Td 52.662037 Tz (para ) Tj 1.419444 0 Td 48.611111 Tz (to ) Tj 0.797222 0 Td 58.333333 Tz (meta ) Tj 1.594444 0 Td 47.727273 Tz (Substituent ) Tj 3.325 0 Td 48.611111 Tz (positions ) Tj 2.838889 0 Td 48.611111 Tz (regardless ) Tj 3.111111 0 Td 58.333333 Tz (of ) Tj 0.777778 0 Td 50.771605 Tz (the ) Tj 1.108333 0 Td 51.851852 Tz (Substitu ) Tj 51.428571 0 0 51.428571 0 377.182999 Tm 6.358333 0 Td 49.691358 Tz (ent ) Tj 0.991667 0 Td 47.314815 Tz (type. ) Tj 1.536111 0 Td 54.282407 Tz (This ) Tj 1.438889 0 Td 51.041667 Tz (suggests ) Tj 2.547222 0 Td 46.990741 Tz (that ) Tj 1.244444 0 Td 59.143519 Tz (meta ) Tj 1.536111 0 Td 47.260802 Tz (Substituents ) Tj 3.519444 0 Td 50.771605 Tz (are ) Tj 1.011111 0 Td 49.691358 Tz (preferred ) Tj 2.819444 0 Td 47.530864 Tz (for ) Tj 48.571429 0 0 48.571429 0 337 Tm 6.752941 0 Td 43.627451 Tz (steric, ) Tj 2.120588 0 Td 50.898693 Tz (rather ) Tj 2.079412 0 Td 54.044118 Tz (than ) Tj 1.585294 0 Td 50.441176 Tz (electronic ) Tj 3.314706 0 Td 51.89951 Tz (reasons. ) Tj 2.779412 0 Td 58.823529 Tz (Second, ) Tj 2.738235 0 Td 49.754902 Tz (in ) Tj 0.864706 0 Td 53.75817 Tz (the ) Tj 1.276471 0 Td 71.20098 Tz (meta ) Tj 51.428571 0 0 51.428571 0 294.363184 Tm 6.377778 0 Td 47.727273 Tz (substituted ) Tj 3.383333 0 Td 45.37037 Tz (series ) Tj 1.886111 0 Td 46.666667 Tz (inhibition ) Tj 3.052778 0 Td 55.497685 Tz (improves ) Tj 2.936111 0 Td 43.75 Tz (in ) Tj 0.797222 0 Td 48.611111 Tz (the ) Tj 1.069444 0 Td 53.148148 Tz (order ) Tj 1.788889 0 Td 59.953704 Tz (of ) Tj 0.855556 0 Td 69.675926 Tz (meth ) Tj 51.428571 0 0 51.428571 0 253.886199 Tm 6.358333 0 Td 51.041667 Tz (oxy, ) Tj 1.438889 0 Td 44.907407 Tz (fluoro, ) Tj 2.080556 0 Td 48.611111 Tz (chloro, ) Tj 2.255556 0 Td 47.314815 Tz (iodo, ) Tj 1.633333 0 Td 47.59838 Tz (trifluoromethyl. ) Tj 4.744444 0 Td 54.282407 Tz (This ) Tj 1.497222 0 Td 51.851852 Tz (order ) Tj 1.75 0 Td 42.939815 Tz (reflects ) Tj 51.428571 0 0 51.428571 0 211.008568 Tm 6.358333 0 Td 49.074074 Tz (neither ) Tj 2.255556 0 Td 46.990741 Tz (size ) Tj 1.380556 0 Td 54.012346 Tz (nor ) Tj 1.166667 0 Td 47.638889 Tz (electronic ) Tj 3.111111 0 Td 49.151235 Tz (trends ) Tj 1.983333 0 Td 66.759259 Tz (among ) Tj 2.236111 0 Td 49.907407 Tz (these ) Tj 1.711111 0 Td 46.118234 Tz (substituents. ) Tj 51.428571 0 0 51.428571 0 170.686717 Tm 6.377778 0 Td 52.662037 Tz (Five ) Tj 1.380556 0 Td 62.294239 Tz (compounds ) Tj 3.538889 0 Td 42.12963 Tz (\(7, ) Tj 0.991667 0 Td 46.450617 Tz (11, ) Tj 1.069444 0 Td 45.37037 Tz (18, ) Tj 0.991667 0 Td 58.333333 Tz (29 ) Tj 0.836111 0 Td 60.493827 Tz (and ) Tj 1.225 0 Td 54.012346 Tz (31\) ) Tj 1.108333 0 Td 59.143519 Tz (were ) Tj 1.575 0 Td 43.75 Tz (at ) Tj 0.680556 0 Td 44.722222 Tz (least ) Tj 1.477778 0 Td 48.611111 Tz (as ) Tj 0.738889 0 Td 51.311728 Tz (potent ) Tj 30 0 0 30 0 1091 Tm 41.566667 0 Td 80.555556 Tz (45 ) Tj 30 0 0 30 0 883 Tm 41.6 0 Td 80.555556 Tz (50 ) Tj 30 0 0 30 0 675 Tm 41.6 0 Td 77.777778 Tz (55 ) Tj 30 0 0 30 0 467 Tm 41.633333 0 Td 77.777778 Tz (60 ) Tj 30 0 0 30 0 259 Tm 41.633333 0 Td 75 Tz (65 ) Tj 51.428571 0 0 51.428571 0 1054.652687 Tm 25.297222 0 Td 50.231481 Tz (as ) Tj 0.875 0 Td 49.691358 Tz (the ) Tj 1.166667 0 Td 51.041667 Tz (lead ) Tj 1.497222 0 Td 64.00463 Tz (compound ) Tj 3.363889 0 Td 40.509259 Tz (\(1\). ) Tj 1.263889 0 Td 57.037037 Tz (Three ) Tj 1.963889 0 Td 58.333333 Tz (of ) Tj 0.875 0 Td 50.771605 Tz (the ) Tj 1.205556 0 Td 58.333333 Tz (most ) Tj 1.652778 0 Td 51.311728 Tz (potent ) Tj 2.1 0 Td 83.179012 Tz (com ) Tj 51.428571 0 0 51.428571 0 1011.604871 Tm 25.297222 0 Td 57.79321 Tz (pounds ) Tj 2.430556 0 Td 58.333333 Tz (had ) Tj 1.380556 0 Td 58.333333 Tz (one ) Tj 1.380556 0 Td 48.611111 Tz (\(11 ) Tj 1.302778 0 Td 58.333333 Tz (and ) Tj 1.361111 0 Td 55.092593 Tz (31\) ) Tj 1.322222 0 Td 51.851852 Tz (or ) Tj 0.952778 0 Td 58.333333 Tz (two ) Tj 1.380556 0 Td 50.231481 Tz (\(18\) ) Tj 1.555556 0 Td 48.82716 Tz (trifluoromethyl ) Tj 51.428571 0 0 51.428571 0 967.409326 Tm 25.297222 0 Td 51.388889 Tz (groups, ) Tj 2.45 0 Td 48.287037 Tz (consistent ) Tj 3.169444 0 Td 52.662037 Tz (with ) Tj 1.555556 0 Td 49.691358 Tz (the ) Tj 1.147222 0 Td 48.611111 Tz (finding ) Tj 2.313889 0 Td 46.990741 Tz (that ) Tj 1.361111 0 Td 43.75 Tz (this ) Tj 1.341667 0 Td 38.888889 Tz (is ) Tj 0.719444 0 Td 50.771605 Tz (the ) Tj 1.205556 0 Td 52.314815 Tz (optimal ) Tj 51.428571 0 0 51.428571 0 922.651106 Tm 25.316667 0 Td 47.727273 Tz (Substituent ) Tj 3.363889 0 Td 52.662037 Tz (type ) Tj 1.497222 0 Td 66.759259 Tz (among ) Tj 2.216667 0 Td 50.771605 Tz (the ) Tj 1.186111 0 Td 57.523148 Tz (meta ) Tj 1.613889 0 Td 45.910494 Tz (series ) Tj 1.905556 0 Td 56.712963 Tz (of ) Tj 0.894444 0 Td 53.148148 Tz (monosubstituted ) Tj 51.428571 0 0 51.428571 0 879.490566 Tm 25.297222 0 Td 49.421296 Tz (analogs. ) Tj 2.547222 0 Td 48.611111 Tz (In ) Tj 0.680556 0 Td 48.611111 Tz (contrast ) Tj 2.411111 0 Td 46.990741 Tz (to ) Tj 0.719444 0 Td 48.611111 Tz (the ) Tj 0.991667 0 Td 57.523148 Tz (improved ) Tj 2.858333 0 Td 46.990741 Tz (inhibition ) Tj 2.975 0 Td 54.282407 Tz (observed ) Tj 2.722222 0 Td 65.625 Tz (when ) Tj 51.428571 0 0 51.428571 0 835.04557 Tm 25.297222 0 Td 49.826389 Tz (chlorine ) Tj 2.625 0 Td 54.6875 Tz (occupied ) Tj 2.858333 0 Td 53.472222 Tz (both ) Tj 1.536111 0 Td 42.12963 Tz (\(1, ) Tj 1.030556 0 Td 65.462963 Tz (K=1.6 ) Tj 2.275 0 Td 66.975309 Tz (uM\) ) Tj 1.438889 0 Td 49.074074 Tz (instead ) Tj 2.275 0 Td 59.953704 Tz (of ) Tj 0.816667 0 Td 54.282407 Tz (only ) Tj 1.555556 0 Td 58.333333 Tz (one ) Tj 51.428571 0 0 51.428571 0 794.321295 Tm 25.316667 0 Td 46.990741 Tz (\(14, ) Tj 1.341667 0 Td 65.462963 Tz (K=2.5 ) Tj 2.352778 0 Td 57.253086 Tz (LM\) ) Tj 1.225 0 Td 56.712963 Tz (of ) Tj 0.758333 0 Td 50.771605 Tz (the ) Tj 1.108333 0 Td 58.333333 Tz (meta ) Tj 1.555556 0 Td 46.666667 Tz (positions, ) Tj 3.013889 0 Td 51.851852 Tz (a ) Tj 0.505556 0 Td 48.070988 Tz (single ) Tj 1.925 0 Td 50.771605 Tz (meta-trifluo ) Tj 51.428571 0 0 51.428571 0 752.905207 Tm 25.297222 0 Td 53.877315 Tz (romethyl ) Tj 2.975 0 Td 47.800926 Tz (\(11, ) Tj 1.516667 0 Td 64.274691 Tz (K=0.03 ) Tj 2.722222 0 Td 68.055556 Tz (uM\) ) Tj 1.575 0 Td 61.574074 Tz (was ) Tj 1.438889 0 Td 50.05144 Tz (preferred ) Tj 3.013889 0 Td 55.092593 Tz (over ) Tj 1.652778 0 Td 58.333333 Tz (two ) Tj 1.438889 0 Td 46.180556 Tz (\(18, ) Tj 52.857143 0 0 52.857143 0 711.013366 Tm 24.632432 0 Td 63.063063 Tz (K=0.16 ) Tj 2.497297 0 Td 55.18018 Tz (uM\), ) Tj 1.475676 0 Td 52.342342 Tz (Table ) Tj 1.759459 0 Td 39.414414 Tz (1. ) Tj 0.662162 0 Td 47.297297 Tz (In ) Tj 0.718919 0 Td 40.36036 Tz (fact, ) Tj 1.4 0 Td 48.873874 Tz (meta-trifluoromethyl ) Tj 6.054054 0 Td 48.873874 Tz (\(11\) ) Tj 1.286486 0 Td 62.012012 Tz (was ) Tj 51.428571 0 0 51.428571 0 669.549561 Tm 25.316667 0 Td 50.462963 Tz (53-fold ) Tj 2.352778 0 Td 62.384259 Tz (more ) Tj 1.691667 0 Td 51.311728 Tz (potent ) Tj 2.061111 0 Td 51.041667 Tz (than ) Tj 1.458333 0 Td 49.691358 Tz (the ) Tj 1.108333 0 Td 51.851852 Tz (lead ) Tj 1.419444 0 Td 64.409722 Tz (compound ) Tj 3.305556 0 Td 54.444444 Tz (while ) Tj 1.866667 0 Td 48.611111 Tz (the ) Tj 1.108333 0 Td 59.41358 Tz (dis ) Tj 51.428571 0 0 51.428571 0 629.69378 Tm 25.277778 0 Td 48.287037 Tz (ubstituted ) Tj 3.072222 0 Td 48.611111 Tz (trifluoromethyl ) Tj 4.55 0 Td 50.231481 Tz (\(18\) ) Tj 1.361111 0 Td 61.574074 Tz (was ) Tj 1.263889 0 Td 53.472222 Tz (only ) Tj 1.536111 0 Td 49.074074 Tz (10-fold ) Tj 2.255556 0 Td 61.574074 Tz (more ) Tj 1.613889 0 Td 51.311728 Tz (potent ) Tj 51.428571 0 0 51.428571 0 585.240537 Tm 25.277778 0 Td 52.662037 Tz (than ) Tj 1.419444 0 Td 49.691358 Tz (the ) Tj 1.05 0 Td 45.37037 Tz (lead. ) Tj 1.497222 0 Td 53.472222 Tz (This ) Tj 1.419444 0 Td 51.446759 Tz (suggests ) Tj 2.605556 0 Td 46.180556 Tz (that ) Tj 1.263889 0 Td 57.253086 Tz (one ) Tj 1.166667 0 Td 55.092593 Tz (of ) Tj 0.738889 0 Td 50.771605 Tz (the ) Tj 1.030556 0 Td 60.493827 Tz (two ) Tj 1.263889 0 Td 56.712963 Tz (meta ) Tj 1.536111 0 Td 51.851852 Tz (Substitu ) Tj 51.428571 0 0 51.428571 0 545.736646 Tm 25.297222 0 Td 48.611111 Tz (ents ) Tj 1.361111 0 Td 38.888889 Tz (is ) Tj 0.641667 0 Td 50 Tz (located ) Tj 2.294444 0 Td 45.37037 Tz (in ) Tj 0.719444 0 Td 55.092593 Tz (a ) Tj 0.525 0 Td 46.616809 Tz (Substantially ) Tj 3.830556 0 Td 47.530864 Tz (larger ) Tj 1.847222 0 Td 54.552469 Tz (pocket ) Tj 2.1 0 Td 51.851852 Tz (than ) Tj 1.438889 0 Td 49.691358 Tz (the ) Tj 1.088889 0 Td 44.290123 Tz (other. ) Tj 51.428571 0 0 51.428571 0 503.617414 Tm 26.016667 0 Td 58.333333 Tz (These ) Tj 1.944444 0 Td 52.777778 Tz (analogs ) Tj 2.430556 0 Td 58.333333 Tz (from ) Tj 1.594444 0 Td 51.851852 Tz (Tables ) Tj 2.177778 0 Td 35.648148 Tz (1 ) Tj 0.486111 0 Td 59.41358 Tz (and ) Tj 1.263889 0 Td 58.333333 Tz (2 ) Tj 0.583333 0 Td 49.421296 Tz (thus ) Tj 1.380556 0 Td 54.282407 Tz (provided ) Tj 2.8 0 Td 49.537037 Tz (diverse ) Tj 51.428571 0 0 51.428571 0 460.903382 Tm 25.316667 0 Td 47.727273 Tz (Substituent ) Tj 3.286111 0 Td 51.203704 Tz (types ) Tj 1.672222 0 Td 60.493827 Tz (and ) Tj 1.244444 0 Td 47.260802 Tz (Substitution ) Tj 3.538889 0 Td 47.800926 Tz (patterns ) Tj 2.469444 0 Td 46.990741 Tz (to ) Tj 0.738889 0 Td 50.555556 Tz (serve ) Tj 1.652778 0 Td 51.851852 Tz (as ) Tj 0.758333 0 Td 58.333333 Tz (a ) Tj 0.505556 0 Td 52.5 Tz (train ) Tj 51.428571 0 0 51.428571 0 422.365508 Tm 25.297222 0 Td 51.851852 Tz (ing ) Tj 1.225 0 Td 45.37037 Tz (set ) Tj 1.108333 0 Td 47.395833 Tz (suitable ) Tj 2.547222 0 Td 49.691358 Tz (for ) Tj 1.166667 0 Td 45.775463 Tz (specific ) Tj 2.488889 0 Td 45.37037 Tz (activity ) Tj 2.469444 0 Td 48.935185 Tz (prediction ) Tj 3.266667 0 Td 50.771605 Tz (within ) Tj 2.138889 0 Td 43.75 Tz (this ) Tj 51.428571 0 0 51.428571 0 378.914355 Tm 25.316667 0 Td 77.777778 Tz (SAR ) Tj 1.555556 0 Td 45.910494 Tz (series ) Tj 1.847222 0 Td 45.37037 Tz (\(as ) Tj 0.991667 0 Td 51.041667 Tz (well ) Tj 1.380556 0 Td 51.851852 Tz (as ) Tj 0.797222 0 Td 46.8107 Tz (potential ) Tj 2.702778 0 Td 50.771605 Tz (intermediate ) Tj 3.811111 0 Td 61.934156 Tz (compounds ) Tj 3.519444 0 Td 48.611111 Tz (for ) Tj 51.428571 0 0 51.428571 0 337.368932 Tm 25.297222 0 Td 47.685185 Tz (further ) Tj 2.216667 0 Td 45.37037 Tz (reactions\). ) Tj 3.208333 0 Td 63.734568 Tz (The ) Tj 1.361111 0 Td 46.8107 Tz (resulting ) Tj 2.741667 0 Td 52.777778 Tz (analogs ) Tj 2.430556 0 Td 59.143519 Tz (were ) Tj 1.613889 0 Td 59.548611 Tz (examined ) Tj 3.072222 0 Td 47.530864 Tz (for ) Tj 51.428571 0 0 51.428571 0 295.403846 Tm 25.277778 0 Td 46.018519 Tz (their ) Tj 1.477778 0 Td 43.981481 Tz (ability ) Tj 2.022222 0 Td 46.990741 Tz (to ) Tj 0.7 0 Td 44.907407 Tz (inhibit ) Tj 2.022222 0 Td 59.41358 Tz (ATX-mediated ) Tj 4.413889 0 Td 50.231481 Tz (hydrolysis ) Tj 3.169444 0 Td 55.092593 Tz (of ) Tj 0.738889 0 Td 56.712963 Tz (FS-3 ) Tj 1.536111 0 Td 45.37037 Tz (at ) Tj 0.758333 0 Td 53.472222 Tz (10 ) Tj 51.428571 0 0 51.428571 0 253.455863 Tm 25.355556 0 Td 61.574074 Tz (uM. ) Tj 1.458333 0 Td 51.851852 Tz (Likewise, ) Tj 3.091667 0 Td 55.902778 Tz (each ) Tj 1.633333 0 Td 54.552469 Tz (analog ) Tj 2.294444 0 Td 60.493827 Tz (was ) Tj 1.380556 0 Td 48.070988 Tz (tested ) Tj 2.022222 0 Td 46.990741 Tz (in ) Tj 0.855556 0 Td 50.771605 Tz (the ) Tj 1.205556 0 Td 53.472222 Tz (presence ) Tj 2.877778 0 Td 56.712963 Tz (of ) Tj 51.428571 0 0 51.428571 0 215.112644 Tm 25.297222 0 Td 51.131687 Tz (carboxyfluorescein ) Tj 5.658333 0 Td 47.800926 Tz (\(the ) Tj 1.244444 0 Td 53.703704 Tz (product ) Tj 2.372222 0 Td 56.712963 Tz (of ) Tj 0.758333 0 Td 59.41358 Tz (ATX-mediated ) Tj 4.394444 0 Td 50.555556 Tz (hydrolysis ) Tj 51.428571 0 0 51.428571 0 171.453446 Tm 25.297222 0 Td 56.712963 Tz (of ) Tj 0.758333 0 Td 55.092593 Tz (FS-3\) ) Tj 1.808333 0 Td 45.37037 Tz (to ) Tj 0.7 0 Td 46.585648 Tz (identify ) Tj 2.391667 0 Td 46.018519 Tz (false ) Tj 1.516667 0 Td 47.800926 Tz (positive ) Tj 2.430556 0 Td 50.231481 Tz (or ) Tj 0.758333 0 Td 50.231481 Tz (negative ) Tj 2.566667 0 Td 42.12963 Tz (results. ) Tj 2.216667 0 Td 64.814815 Tz (None ) Tj 1.711111 0 Td 58.333333 Tz (of ) Tj 1.428571 0 0 1.428571 0 2874 Tm 369.6 0 Td 116.666667 Tz ( ) Tj ET Q endstream endobj 300 0 obj << /Length 1 >> stream q endstream endobj 301 0 obj << /Length 43721 >> stream Q q 0.24 0 0 0.24 0 0 cm BT /F1 1 Tf 3 Tr 62.857143 0 0 62.857143 0 3023 Tm 17.325 0 Td 83.522727 Tz (US ) Tj 1.240909 0 Td 57.154882 Tz (8,497,371 ) Tj 3.388636 0 Td 74.242424 Tz (B2 ) Tj 52.857143 0 0 52.857143 0 2968 Tm 14.208108 0 Td 77.252252 Tz (25 ) Tj 51.428571 0 0 51.428571 0 2918.687805 Tm 6.338889 0 Td 50.771605 Tz (the ) Tj 1.205556 0 Td 52.777778 Tz (analogs ) Tj 2.547222 0 Td 46.990741 Tz (tested ) Tj 2.002778 0 Td 45.619658 Tz (significantly ) Tj 3.888889 0 Td 47.685185 Tz (altered ) Tj 2.313889 0 Td 51.49177 Tz (carboxyfluorescein ) Tj 51.428571 0 0 51.428571 0 2873.149533 Tm 6.358333 0 Td 48.611111 Tz (fluorescence. ) Tj 3.966667 0 Td 64.814815 Tz (Compounds ) Tj 3.675 0 Td 50.87963 Tz (containing ) Tj 3.227778 0 Td 57.523148 Tz (meta ) Tj 1.536111 0 Td 47.530864 Tz (Substituents ) Tj 3.558333 0 Td 83.179012 Tz (dem ) Tj 51.428571 0 0 51.428571 0 2828.245963 Tm 6.358333 0 Td 49.691358 Tz (onstrated ) Tj 2.897222 0 Td 51.49177 Tz (responses ) Tj 2.994444 0 Td 45.37037 Tz (in ) Tj 0.738889 0 Td 50.771605 Tz (the ) Tj 1.088889 0 Td 53.796296 Tz (range ) Tj 1.769444 0 Td 58.333333 Tz (of ) Tj 0.855556 0 Td 70.216049 Tz (60% ) Tj 1.477778 0 Td 45.37037 Tz (to ) Tj 0.797222 0 Td 68.055556 Tz (100% ) Tj 1.847222 0 Td 45.075758 Tz (inhibition. ) Tj 51.428571 0 0 51.428571 0 2787.484587 Tm 6.358333 0 Td 67.650463 Tz (Compound ) Tj 3.480556 0 Td 45.37037 Tz (11 ) Tj 0.836111 0 Td 51.851852 Tz (with ) Tj 1.4 0 Td 58.333333 Tz (a ) Tj 0.486111 0 Td 49.04321 Tz (trifluoromethyl ) Tj 4.588889 0 Td 55.740741 Tz (group ) Tj 1.886111 0 Td 43.75 Tz (in ) Tj 0.680556 0 Td 50.771605 Tz (the ) Tj 1.108333 0 Td 57.523148 Tz (meta ) Tj 1.516667 0 Td 61.574074 Tz (posi ) Tj 52.857143 0 0 52.857143 0 2740.103448 Tm 6.167568 0 Td 42.882883 Tz (tion, ) Tj 1.475676 0 Td 50.45045 Tz (yielded ) Tj 2.364865 0 Td 66.216216 Tz (100% ) Tj 1.816216 0 Td 45.405405 Tz (inhibition ) Tj 2.932432 0 Td 58.858859 Tz (and ) Tj 1.248649 0 Td 59.90991 Tz (was ) Tj 1.305405 0 Td 52.972973 Tz (determined ) Tj 3.405405 0 Td 42.567568 Tz (to ) Tj 0.718919 0 Td 58.333333 Tz (be ) Tj 0.889189 0 Td 49.399399 Tz (the ) Tj 1.437838 0 Td 37.837838 Tz (5 ) Tj 51.428571 0 0 51.428571 0 2698.031175 Tm 6.338889 0 Td 49.421296 Tz (best ) Tj 1.361111 0 Td 47.685185 Tz (overall ) Tj 2.197222 0 Td 64.00463 Tz (compound ) Tj 3.266667 0 Td 43.981481 Tz (tested. ) Tj 51.428571 0 0 51.428571 0 2652.816273 Tm 7.097222 0 Td 62.654321 Tz (The ) Tj 1.438889 0 Td 43.376068 Tz (selectivities ) Tj 3.675 0 Td 59.953704 Tz (of ) Tj 0.913889 0 Td 49.691358 Tz (the ) Tj 1.166667 0 Td 48.971193 Tz (inventive ) Tj 2.916667 0 Td 62.294239 Tz (compounds ) Tj 3.675 0 Td 53.472222 Tz (\(and ) Tj 1.536111 0 Td 77.777778 Tz (ATX ) Tj 51.428571 0 0 51.428571 0 2608 Tm 6.358333 0 Td 46.254209 Tz (inhibitors\) ) Tj 3.227778 0 Td 43.75 Tz (3, ) Tj 0.719444 0 Td 43.75 Tz (7, ) Tj 0.797222 0 Td 46.450617 Tz (11, ) Tj 1.108333 0 Td 46.450617 Tz (13, ) Tj 1.088889 0 Td 45.37037 Tz (14, ) Tj 1.088889 0 Td 46.450617 Tz (18, ) Tj 1.108333 0 Td 45.37037 Tz (19, ) Tj 1.030556 0 Td 49.691358 Tz (20, ) Tj 1.088889 0 Td 49.691358 Tz (22, ) Tj 1.069444 0 Td 50.771605 Tz (23, ) Tj 1.127778 0 Td 49.691358 Tz (25, ) Tj 1.088889 0 Td 49.691358 Tz (27, ) Tj 1.069444 0 Td 51.851852 Tz (28, ) Tj 1.127778 0 Td 58.333333 Tz (29 ) Tj 51.428571 0 0 51.428571 0 2565.538841 Tm 6.358333 0 Td 58.333333 Tz (and ) Tj 1.283333 0 Td 50.771605 Tz (31, ) Tj 1.147222 0 Td 39.969136 Tz (all ) Tj 0.972222 0 Td 58.333333 Tz (of ) Tj 0.836111 0 Td 58.981481 Tz (which ) Tj 2.022222 0 Td 47.890947 Tz (inhibited ) Tj 2.8 0 Td 59.683642 Tz (ATX-mediated ) Tj 4.511111 0 Td 50.555556 Tz (hydrolysis ) Tj 3.286111 0 Td 58.333333 Tz (of ) Tj 49.642857 0 0 49.642857 0 2522.221228 Tm 6.607194 0 Td 58.752998 Tz (FS-3 ) Tj 1.71223 0 Td 63.788969 Tz (by ) Tj 1.107914 0 Td 80.57554 Tz (250% ) Tj 2.215827 0 Td 48.681055 Tz (at ) Tj 0.886331 0 Td 49.240608 Tz (single ) Tj 2.054676 0 Td 55.731415 Tz (doses ) Tj 1.953957 0 Td 62.110312 Tz (of ) Tj 0.98705 0 Td 58.752998 Tz (10 ) Tj 1.007194 0 Td 66.027178 Tz (uM, ) Tj 1.490647 0 Td 61.270983 Tz (were ) Tj 1.732374 0 Td 61.690647 Tz (examined ) Tj 3.42446 0 Td 45.323741 Tz (10 ) Tj 51.428571 0 0 51.428571 0 2479.228091 Tm 6.358333 0 Td 49.537037 Tz (against ) Tj 2.197222 0 Td 69.675926 Tz (NPP6 ) Tj 1.847222 0 Td 58.333333 Tz (and ) Tj 1.205556 0 Td 70.486111 Tz (NPP7 ) Tj 1.808333 0 Td 43.209877 Tz (\(in ) Tj 0.952778 0 Td 54.768519 Tz (accordance ) Tj 3.441667 0 Td 52.662037 Tz (with ) Tj 1.4 0 Td 50.771605 Tz (the ) Tj 1.030556 0 Td 42.939815 Tz (test ) Tj 1.147222 0 Td 50.636574 Tz (protocol ) Tj 51.428571 0 0 51.428571 0 2437.144578 Tm 6.358333 0 Td 53.877315 Tz (provided ) Tj 2.741667 0 Td 51.388889 Tz (above\), ) Tj 2.372222 0 Td 48.611111 Tz (the ) Tj 1.030556 0 Td 54.282407 Tz (only ) Tj 1.497222 0 Td 50.555556 Tz (other ) Tj 1.691667 0 Td 64.166667 Tz (known ) Tj 2.138889 0 Td 46.585648 Tz (lipid-preferring ) Tj 4.686111 0 Td 72.376543 Tz (NPP ) Tj 51.428571 0 0 51.428571 0 2391.875158 Tm 6.358333 0 Td 50.05144 Tz (isoforms. ) Tj 3.033333 0 Td 65.625 Tz (None ) Tj 1.827778 0 Td 61.574074 Tz (of ) Tj 0.913889 0 Td 50.771605 Tz (the ) Tj 1.166667 0 Td 62.294239 Tz (compounds ) Tj 3.655556 0 Td 49.016204 Tz (affected ) Tj 2.625 0 Td 49.691358 Tz (the ) Tj 1.166667 0 Td 45.37037 Tz (activity ) Tj 2.469444 0 Td 58.333333 Tz (of ) Tj 51.428571 0 0 51.428571 0 2348.996301 Tm 6.338889 0 Td 72.106481 Tz (NPP6 ) Tj 1.886111 0 Td 51.851852 Tz (or ) Tj 0.758333 0 Td 71.296296 Tz (NPP7 ) Tj 1.866667 0 Td 52.5 Tz (\(FIG. ) Tj 1.75 0 Td 43.209877 Tz (6\). ) Tj 0.991667 0 Td 51.131687 Tz (Likewise, ) Tj 2.936111 0 Td 54.282407 Tz (each ) Tj 1.497222 0 Td 54.552469 Tz (analog ) Tj 2.1 0 Td 60.493827 Tz (was ) Tj 1.302778 0 Td 45.910494 Tz (tested ) Tj 1.847222 0 Td 48.611111 Tz (in ) Tj 51.428571 0 0 51.428571 0 2310.245283 Tm 6.338889 0 Td 50.771605 Tz (the ) Tj 1.069444 0 Td 53.472222 Tz (presence ) Tj 2.741667 0 Td 56.712963 Tz (of ) Tj 0.758333 0 Td 50.854701 Tz (p-nitrophenol ) Tj 4.161111 0 Td 46.990741 Tz (\(the ) Tj 1.302778 0 Td 52.777778 Tz (product ) Tj 2.391667 0 Td 58.333333 Tz (of ) Tj 0.777778 0 Td 59.953704 Tz (ATX-mediated ) Tj 51.428571 0 0 51.428571 0 2272.381008 Tm 6.338889 0 Td 50.555556 Tz (hydrolysis ) Tj 3.286111 0 Td 59.953704 Tz (of ) Tj 0.855556 0 Td 52.067901 Tz (p-nitrophenylphosphorylcholine ) Tj 9.644444 0 Td 60.358796 Tz (\(pNPPC\)\) ) Tj 3.130556 0 Td 46.990741 Tz (to ) Tj 51.428571 0 0 51.428571 0 2225.28436 Tm 6.358333 0 Td 50.411523 Tz (eliminate ) Tj 2.819444 0 Td 50.771605 Tz (the ) Tj 1.030556 0 Td 56.17284 Tz (chance ) Tj 2.138889 0 Td 56.712963 Tz (of ) Tj 0.758333 0 Td 45.37037 Tz (false ) Tj 1.477778 0 Td 47.395833 Tz (positive ) Tj 2.411111 0 Td 51.851852 Tz (or ) Tj 0.738889 0 Td 44.722222 Tz (false ) Tj 1.477778 0 Td 50.231481 Tz (negative ) Tj 2.527778 0 Td 42.939815 Tz (results. ) Tj 51.428571 0 0 51.428571 0 2183.860158 Tm 6.358333 0 Td 66.435185 Tz (None ) Tj 1.886111 0 Td 55.092593 Tz (of ) Tj 0.855556 0 Td 49.691358 Tz (the ) Tj 1.147222 0 Td 53.240741 Tz (analogs ) Tj 2.527778 0 Td 47.530864 Tz (tested ) Tj 1.983333 0 Td 58.333333 Tz (had ) Tj 1.322222 0 Td 55.092593 Tz (a ) Tj 0.622222 0 Td 45.959596 Tz (significant ) Tj 3.305556 0 Td 45.910494 Tz (affect ) Tj 1.944444 0 Td 56.712963 Tz (on ) Tj 0.991667 0 Td 49.691358 Tz (the ) Tj 51.428571 0 0 51.428571 0 2145.021965 Tm 6.358333 0 Td 50.605413 Tz (p-nitrophenol ) Tj 4.063889 0 Td 52.441077 Tz (absorbance. ) Tj 3.597222 0 Td 58.981481 Tz (FIG.3 ) Tj 1.905556 0 Td 52.256944 Tz (provides ) Tj 2.625 0 Td 55.092593 Tz (a ) Tj 0.466667 0 Td 48.842593 Tz (representation ) Tj 4.2 0 Td 58.333333 Tz (of ) Tj 51.428571 0 0 51.428571 0 2100.875158 Tm 6.338889 0 Td 50.771605 Tz (the ) Tj 1.147222 0 Td 69.675926 Tz (NPP6 ) Tj 1.905556 0 Td 58.333333 Tz (and ) Tj 1.302778 0 Td 69.675926 Tz (NPP7 ) Tj 1.905556 0 Td 48.070988 Tz (single ) Tj 1.944444 0 Td 55.902778 Tz (dose ) Tj 1.575 0 Td 52.662037 Tz (response ) Tj 2.761111 0 Td 42.777778 Tz (plot. ) Tj 1.516667 0 Td 62.5 Tz (Columns ) Tj 2.858333 0 Td 50.231481 Tz (in ) Tj 51.428571 0 0 51.428571 0 2060.244284 Tm 6.358333 0 Td 52.662037 Tz (grey ) Tj 1.477778 0 Td 48.611111 Tz (represent ) Tj 2.761111 0 Td 49.691358 Tz (the ) Tj 1.05 0 Td 53.703704 Tz (isoform ) Tj 2.391667 0 Td 62.87037 Tz (NPP6, ) Tj 2.041667 0 Td 58.333333 Tz (columns ) Tj 2.605556 0 Td 45.37037 Tz (in ) Tj 0.738889 0 Td 52.5 Tz (white ) Tj 1.75 0 Td 49.331276 Tz (represent ) Tj 51.428571 0 0 51.428571 0 2016.677419 Tm 6.338889 0 Td 50.771605 Tz (the ) Tj 1.147222 0 Td 52.777778 Tz (isoform ) Tj 2.45 0 Td 70.486111 Tz (NPP7 ) Tj 1.886111 0 Td 61.574074 Tz (and ) Tj 1.283333 0 Td 49.691358 Tz (the ) Tj 1.088889 0 Td 58.796296 Tz (columns ) Tj 2.683333 0 Td 46.990741 Tz (in ) Tj 0.777778 0 Td 53.796296 Tz (black ) Tj 1.769444 0 Td 50.771605 Tz (are ) Tj 1.108333 0 Td 54.768519 Tz (p-nitrophe ) Tj 40 0 0 40 0 1982 Tm 8.175 0 Td 63.888889 Tz (nolate ) Tj 2.525 0 Td 59.259259 Tz (controls. ) Tj 51.428571 0 0 51.428571 0 1934.128625 Tm 7.116667 0 Td 46.990741 Tz (In ) Tj 0.738889 0 Td 47.890947 Tz (addition, ) Tj 2.8 0 Td 52.599715 Tz (dose-response ) Tj 4.277778 0 Td 52.391975 Tz (curves ) Tj 2.080556 0 Td 58.333333 Tz (were ) Tj 1.594444 0 Td 54.768519 Tz (determined ) Tj 3.461111 0 Td 48.611111 Tz (for ) Tj 1.030556 0 Td 39.969136 Tz (all ) Tj 51.428571 0 0 51.428571 0 1892.634146 Tm 6.436111 0 Td 53.472222 Tz (15 ) Tj 0.855556 0 Td 53.240741 Tz (analogs ) Tj 2.469444 0 Td 45.37037 Tz (that ) Tj 1.302778 0 Td 47.170782 Tz (inhibited ) Tj 2.741667 0 Td 60.223765 Tz (ATX-mediated ) Tj 4.55 0 Td 50.231481 Tz (hydrolysis ) Tj 3.208333 0 Td 61.574074 Tz (of ) Tj 0.894444 0 Td 55.902778 Tz (FS-3 ) Tj 51.428571 0 0 51.428571 0 1850.273684 Tm 6.338889 0 Td 61.574074 Tz (by ) Tj 0.913889 0 Td 80.208333 Tz (250% ) Tj 2.061111 0 Td 46.990741 Tz (at ) Tj 0.777778 0 Td 56.712963 Tz (10 ) Tj 0.836111 0 Td 63.734568 Tz (uM. ) Tj 1.341667 0 Td 54.012346 Tz (ICs ) Tj 1.438889 0 Td 49.691358 Tz (values ) Tj 2.002778 0 Td 45.37037 Tz (in ) Tj 0.7 0 Td 55.092593 Tz (a ) Tj 0.486111 0 Td 53.796296 Tz (range ) Tj 1.769444 0 Td 56.712963 Tz (of ) Tj 0.777778 0 Td 59.41358 Tz (900 ) Tj 1.225 0 Td 82.638889 Tz (nM ) Tj 1.166667 0 Td 45.37037 Tz (to ) Tj 0.777778 0 Td 49.421296 Tz (17.7 ) Tj 51.428571 0 0 51.428571 0 1808.747573 Tm 6.416667 0 Td 79.398148 Tz (uM ) Tj 1.108333 0 Td 59.143519 Tz (were ) Tj 1.555556 0 Td 54.282407 Tz (observed ) Tj 2.761111 0 Td 51.851852 Tz (\(FIG. ) Tj 1.730556 0 Td 61.574074 Tz (7 ) Tj 0.486111 0 Td 61.574074 Tz (and ) Tj 1.205556 0 Td 53.796296 Tz (Table ) Tj 1.808333 0 Td 38.888889 Tz (1\). ) Tj 0.875 0 Td 64.814815 Tz (Compounds ) Tj 3.675 0 Td 73.240741 Tz (demon ) Tj 52.857143 0 0 52.857143 0 1766.240055 Tm 6.205405 0 Td 44.538288 Tz (strating ) Tj 2.345946 0 Td 56.756757 Tz (an ) Tj 0.945946 0 Td 51.501502 Tz (ICs ) Tj 1.456757 0 Td 42.567568 Tz (less ) Tj 1.305405 0 Td 49.662162 Tz (than ) Tj 1.532432 0 Td 50.45045 Tz (15 ) Tj 1.22973 0 Td 100.900901 Tz (M ) Tj 0.851351 0 Td 57.545045 Tz (were ) Tj 1.627027 0 Td 46.396396 Tz (further ) Tj 2.156757 0 Td 57.150901 Tz (examined ) Tj 2.97027 0 Td 45.720721 Tz (to ) Tj 62.857143 0 0 62.857143 0 1716 Tm 5.202273 0 Td 44.486532 Tz (determine ) Tj 2.561364 0 Td 37.651515 Tz (their ) Tj 1.304545 0 Td 49.200337 Tz (mechanism ) Tj 2.847727 0 Td 50.378788 Tz (of ) Tj 0.7 0 Td 37.362259 Tz (inhibition. ) Tj 2.656818 0 Td 53.030303 Tz (From ) Tj 1.463636 0 Td 36.458333 Tz (this ) Tj 1.034091 0 Td 40.435606 Tz (data ) Tj 1.161364 0 Td 46.401515 Tz (K, ) Tj 51.428571 0 0 51.428571 0 1685.356511 Tm 6.358333 0 Td 50.771605 Tz (values ) Tj 2.1 0 Td 58.333333 Tz (were ) Tj 1.633333 0 Td 48.935185 Tz (calculated ) Tj 3.169444 0 Td 48.611111 Tz (for ) Tj 1.069444 0 Td 55.092593 Tz (each ) Tj 1.555556 0 Td 54.012346 Tz (analog ) Tj 2.158333 0 Td 59.41358 Tz (and ) Tj 1.283333 0 Td 53.877315 Tz (provided ) Tj 2.838889 0 Td 43.75 Tz (in ) Tj 0.777778 0 Td 49.691358 Tz (the ) Tj 52.857143 0 0 52.857143 0 1643.265018 Tm 6.186486 0 Td 51.151151 Tz (following ) Tj 2.894595 0 Td 52.342342 Tz (Table ) Tj 1.721622 0 Td 57.807808 Tz (and ) Tj 1.22973 0 Td 45.720721 Tz (in ) Tj 0.718919 0 Td 48.348348 Tz (the ) Tj 1.021622 0 Td 53.603604 Tz (graph ) Tj 1.797297 0 Td 45.720721 Tz (in ) Tj 0.775676 0 Td 52.027027 Tz (FIG. ) Tj 1.456757 0 Td 42.567568 Tz (4. ) Tj 30 0 0 30 0 2339 Tm 41.666667 0 Td 72.222222 Tz (15 ) Tj 30 0 0 30 0 1923 Tm 41.6 0 Td 77.777778 Tz (25 ) Tj 39.142857 0 0 39.142857 0 1489.178988 Tm 16.529197 0 Td 50.62179 Tz (Substrate ) Tj 2.963504 0 Td 56.417275 Tz (FS-3 ) Tj 1.583942 0 Td 44.708029 Tz (\(1 ) Tj 0.843066 0 Td 51.094891 Tz (LIM\) ) Tj 9.963504 0 Td 59.610706 Tz (35 ) Tj 38.095238 0 0 38.095238 0 1424.369159 Tm 14.51625 0 Td 50.069444 Tz (Inhibitor ) Tj 8.95125 0 Td 56.875 Tz (ICso ) Tj 1.5225 0 Td 51.625 Tz (\(LIM\) ) Tj 30 0 0 30 0 1366 Tm 20.133333 0 Td 77.777778 Tz (7 ) Tj 10.6 0 Td 63.888889 Tz (12.1 ) Tj 30 0 0 30 0 1333 Tm 19.7 0 Td 69.444444 Tz (11 ) Tj 10.333333 0 Td 94.444444 Tz (O.90.3 ) Tj 30 0 0 30 0 1300 Tm 19.7 0 Td 75 Tz (18 ) Tj 10.3 0 Td 105.555556 Tz (44 ) Tj 1.566667 0 Td 27.777778 Tz (- ) Tj 0.766667 0 Td 61.111111 Tz (1.5 ) Tj 30 0 0 30 0 1267 Tm 19.633333 0 Td 80.555556 Tz (29 ) Tj 11.6 0 Td 61.111111 Tz (1.6 ) Tj 30 0 0 30 0 1233 Tm 19.633333 0 Td 75 Tz (31 ) Tj 11.6 0 Td 59.259259 Tz (1.5 ) Tj 30 0 0 30 0 1299 Tm 41.566667 0 Td 83.333333 Tz (40 ) Tj 51.428571 0 0 51.428571 0 1126.14531 Tm 7.097222 0 Td 57.685185 Tz (These ) Tj 1.983333 0 Td 55.092593 Tz (dose ) Tj 1.575 0 Td 52.662037 Tz (response ) Tj 2.741667 0 Td 47.314815 Tz (plots ) Tj 1.691667 0 Td 60.763889 Tz (show ) Tj 1.75 0 Td 44.560185 Tz (that ) Tj 1.302778 0 Td 49.907407 Tz (these ) Tj 1.730556 0 Td 44.560185 Tz (five ) Tj 1.341667 0 Td 48.611111 Tz (inventive ) Tj 51.428571 0 0 51.428571 0 1086.985932 Tm 6.358333 0 Td 61.934156 Tz (compounds ) Tj 3.480556 0 Td 49.691358 Tz (are ) Tj 1.030556 0 Td 60.763889 Tz (more ) Tj 1.575 0 Td 50.771605 Tz (potent ) Tj 1.925 0 Td 51.851852 Tz (than ) Tj 1.361111 0 Td 51.041667 Tz (lead ) Tj 1.341667 0 Td 64.409722 Tz (compound ) Tj 3.15 0 Td 56.712963 Tz (A, ) Tj 0.816667 0 Td 52.211934 Tz (described ) Tj 40 0 0 40 0 1049 Tm 8.175 0 Td 66.666667 Tz (above. ) Tj 51.428571 0 0 51.428571 0 1001.499371 Tm 7.097222 0 Td 53.796296 Tz (Thus, ) Tj 1.788889 0 Td 32.407407 Tz (it ) Tj 0.525 0 Td 37.268519 Tz (is ) Tj 0.622222 0 Td 50.462963 Tz (evident ) Tj 2.255556 0 Td 46.180556 Tz (that ) Tj 1.225 0 Td 49.691358 Tz (the ) Tj 1.05 0 Td 46.759259 Tz (derivatization ) Tj 4.063889 0 Td 56.712963 Tz (of ) Tj 0.758333 0 Td 53.652263 Tz (pipemidic ) Tj 3.033333 0 Td 46.018519 Tz (acid, ) Tj 51.428571 0 0 51.428571 0 961.386503 Tm 6.377778 0 Td 54.282407 Tz (Such ) Tj 1.516667 0 Td 51.851852 Tz (as ) Tj 0.875 0 Td 52.662037 Tz (with ) Tj 1.477778 0 Td 52.083333 Tz (phenylthiourea ) Tj 4.608333 0 Td 47.530864 Tz (reactants ) Tj 2.8 0 Td 53.472222 Tz (with ) Tj 1.536111 0 Td 50 Tz (various ) Tj 2.313889 0 Td 55.555556 Tz (pendant ) Tj 51.428571 0 0 51.428571 0 919.587629 Tm 6.358333 0 Td 54.552469 Tz (groups ) Tj 2.275 0 Td 54.282407 Tz (\(and ) Tj 1.594444 0 Td 64.00463 Tz (some ) Tj 1.808333 0 Td 48.611111 Tz (especially ) Tj 3.227778 0 Td 50.771605 Tz (robust ) Tj 2.1 0 Td 46.990741 Tz (in ) Tj 0.855556 0 Td 76.697531 Tz (ATX ) Tj 1.691667 0 Td 45.37037 Tz (inhibition, ) Tj 3.305556 0 Td 50.231481 Tz (as ) Tj 51.428571 0 0 51.428571 0 877.409639 Tm 6.358333 0 Td 54.444444 Tz (noted ) Tj 1.788889 0 Td 54.552469 Tz (above\) ) Tj 2.158333 0 Td 51.851852 Tz (provides ) Tj 2.663889 0 Td 51.851852 Tz (a ) Tj 0.544444 0 Td 48.611111 Tz (viable ) Tj 1.944444 0 Td 61.033951 Tz (manner ) Tj 2.352778 0 Td 56.712963 Tz (of ) Tj 0.758333 0 Td 49.421296 Tz (reacting ) Tj 2.547222 0 Td 50.771605 Tz (autotaxin ) Tj 51.428571 0 0 51.428571 0 835.613665 Tm 6.358333 0 Td 49.691358 Tz (for ) Tj 1.030556 0 Td 46.666667 Tz (inhibition ) Tj 2.955556 0 Td 56.712963 Tz (of ) Tj 0.797222 0 Td 44.722222 Tz (reactivity ) Tj 2.858333 0 Td 58.333333 Tz (of ) Tj 0.797222 0 Td 53.472222 Tz (such ) Tj 1.458333 0 Td 56.712963 Tz (an ) Tj 0.836111 0 Td 57.87037 Tz (enzyme. ) Tj 2.605556 0 Td 51.851852 Tz (Tables ) Tj 2.1 0 Td 38.888889 Tz (1 ) Tj 0.447222 0 Td 59.41358 Tz (and ) Tj 1.244444 0 Td 55.092593 Tz (2 ) Tj 51.428571 0 0 51.428571 0 797.575179 Tm 6.358333 0 Td 53.240741 Tz (provide ) Tj 2.391667 0 Td 78.858025 Tz (SAR ) Tj 1.594444 0 Td 44.650206 Tz (insights, ) Tj 2.605556 0 Td 50.231481 Tz (lead ) Tj 1.380556 0 Td 63.599537 Tz (compound ) Tj 3.227778 0 Td 50.771605 Tz (optimization ) Tj 3.85 0 Td 50.231481 Tz (data ) Tj 1.341667 0 Td 61.574074 Tz (and ) Tj 51.428571 0 0 51.428571 0 752.128079 Tm 6.358333 0 Td 60.853909 Tz (mechanism ) Tj 3.519444 0 Td 58.333333 Tz (of ) Tj 0.816667 0 Td 46.990741 Tz (inhibition ) Tj 3.072222 0 Td 46.450617 Tz (for ) Tj 1.030556 0 Td 49.691358 Tz (the ) Tj 1.127778 0 Td 58.333333 Tz (most ) Tj 1.575 0 Td 50.771605 Tz (potent ) Tj 2.061111 0 Td 49.421296 Tz (analogs. ) Tj 2.605556 0 Td 91.820988 Tz (Com ) Tj 52.857143 0 0 52.857143 0 710.730083 Tm 6.167568 0 Td 57.807808 Tz (pounds ) Tj 2.175676 0 Td 44.144144 Tz (7, ) Tj 0.7 0 Td 45.195195 Tz (11, ) Tj 0.927027 0 Td 56.756757 Tz (and ) Tj 1.210811 0 Td 53.603604 Tz (18 ) Tj 0.756757 0 Td 58.333333 Tz (were ) Tj 1.475676 0 Td 50.737101 Tz (competitive ) Tj 3.443243 0 Td 53.603604 Tz (ATXinhibitors ) Tj 4.275676 0 Td 52.027027 Tz (with ) Tj 1.4 0 Td 53.603604 Tz (K, ) Tj 51.428571 0 0 51.428571 0 669.210909 Tm 6.358333 0 Td 50.771605 Tz (values ) Tj 1.983333 0 Td 52.777778 Tz (ranging ) Tj 2.333333 0 Td 57.523148 Tz (from ) Tj 1.497222 0 Td 63.194444 Tz (30 ) Tj 0.875 0 Td 43.75 Tz (to ) Tj 0.661111 0 Td 60.493827 Tz (430 ) Tj 1.244444 0 Td 63.734568 Tz (nM. ) Tj 1.263889 0 Td 53.148148 Tz (Thus, ) Tj 1.75 0 Td 49.907407 Tz (these ) Tj 1.613889 0 Td 52.777778 Tz (analogs ) Tj 2.333333 0 Td 49.691358 Tz (are ) Tj 0.991667 0 Td 49.691358 Tz (3.7 ) Tj 51.428571 0 0 51.428571 0 628.780427 Tm 6.338889 0 Td 45.37037 Tz (to ) Tj 0.777778 0 Td 51.851852 Tz (53.3 ) Tj 1.477778 0 Td 51.851852 Tz (times ) Tj 1.788889 0 Td 60.763889 Tz (more ) Tj 1.633333 0 Td 51.851852 Tz (potent ) Tj 2.022222 0 Td 51.851852 Tz (than ) Tj 1.438889 0 Td 49.691358 Tz (the ) Tj 1.088889 0 Td 45.37037 Tz (lead. ) Tj 1.575 0 Td 65.174897 Tz (Compounds ) Tj 3.733333 0 Td 59.953704 Tz (29 ) Tj 0.875 0 Td 60.493827 Tz (and ) Tj 51.428571 0 0 51.428571 0 586.212987 Tm 6.358333 0 Td 55.092593 Tz (31 ) Tj 1.011111 0 Td 58.333333 Tz (were ) Tj 1.652778 0 Td 53.098291 Tz (uncompetitive ) Tj 4.375 0 Td 77.777778 Tz (ATX ) Tj 1.691667 0 Td 45.694444 Tz (inhibitors ) Tj 3.052778 0 Td 52.662037 Tz (with ) Tj 1.575 0 Td 81.018519 Tz (K ) Tj 0.952778 0 Td 49.691358 Tz (values ) Tj 2.080556 0 Td 45.37037 Tz (that ) Tj 51.428571 0 0 51.428571 0 546.960205 Tm 6.338889 0 Td 59.953704 Tz (were ) Tj 1.75 0 Td 53.846154 Tz (approximately ) Tj 4.530556 0 Td 50.555556 Tz (equivalent ) Tj 3.325 0 Td 46.990741 Tz (to ) Tj 0.913889 0 Td 49.691358 Tz (the ) Tj 1.225 0 Td 45.37037 Tz (lead. ) Tj 1.75 0 Td 44.965278 Tz (Finally, ) Tj 2.488889 0 Td 83.179012 Tz (com ) Tj 51.428571 0 0 51.428571 0 502.167568 Tm 6.358333 0 Td 58.333333 Tz (pounds ) Tj 2.391667 0 Td 45.37037 Tz (3, ) Tj 0.933333 0 Td 45.37037 Tz (13, ) Tj 1.166667 0 Td 47.530864 Tz (14, ) Tj 1.147222 0 Td 49.691358 Tz (20, ) Tj 1.225 0 Td 49.691358 Tz (22, ) Tj 1.166667 0 Td 60.493827 Tz (and ) Tj 1.361111 0 Td 59.953704 Tz (28 ) Tj 1.05 0 Td 58.333333 Tz (were ) Tj 1.711111 0 Td 60.925926 Tz (mixed-mode ) Tj 3.888889 0 Td 78.858025 Tz (ATX ) Tj 51.428571 0 0 51.428571 0 460.137107 Tm 6.358333 0 Td 46.018519 Tz (inhibitors ) Tj 2.955556 0 Td 53.472222 Tz (with ) Tj 1.497222 0 Td 81.018519 Tz (K ) Tj 0.855556 0 Td 49.691358 Tz (values ) Tj 2.002778 0 Td 52.314815 Tz (ranging ) Tj 2.372222 0 Td 56.712963 Tz (from ) Tj 1.633333 0 Td 46.450617 Tz (1.7 ) Tj 0.991667 0 Td 46.990741 Tz (to ) Tj 0.797222 0 Td 60.648148 Tz (13.5uM. ) Tj 2.702778 0 Td 54.444444 Tz (Thus, ) Tj 51.428571 0 0 51.428571 0 422.724638 Tm 6.338889 0 Td 50.555556 Tz (these ) Tj 1.672222 0 Td 45.37037 Tz (six ) Tj 0.933333 0 Td 53.240741 Tz (analogs ) Tj 2.411111 0 Td 58.333333 Tz (were ) Tj 1.497222 0 Td 51.851852 Tz (as ) Tj 0.738889 0 Td 51.311728 Tz (potent ) Tj 1.983333 0 Td 48.611111 Tz (as ) Tj 0.758333 0 Td 50.231481 Tz (or ) Tj 0.719444 0 Td 45.868946 Tz (significantly ) Tj 3.752778 0 Td 43.75 Tz (less ) Tj 1.186111 0 Td 51.311728 Tz (potent ) Tj 40 0 0 40 0 384 Tm 8.15 0 Td 67.708333 Tz (than ) Tj 1.9 0 Td 62.5 Tz (the ) Tj 1.35 0 Td 58.333333 Tz (lead. ) Tj 51.428571 0 0 51.428571 0 340.380435 Tm 7.097222 0 Td 49.691358 Tz (Thirty ) Tj 2.080556 0 Td 51.851852 Tz (out ) Tj 1.186111 0 Td 59.953704 Tz (of ) Tj 0.913889 0 Td 59.953704 Tz (70 ) Tj 0.972222 0 Td 47.170782 Tz (potential ) Tj 2.819444 0 Td 52.777778 Tz (analogs ) Tj 2.488889 0 Td 58.333333 Tz (of ) Tj 0.875 0 Td 64.00463 Tz (compound ) Tj 3.422222 0 Td 32.407407 Tz (1 ) Tj 0.563889 0 Td 59.143519 Tz (were ) Tj 51.428571 0 0 51.428571 0 297.489281 Tm 6.377778 0 Td 51.262626 Tz (synthesized ) Tj 3.675 0 Td 55.092593 Tz (based ) Tj 1.944444 0 Td 58.333333 Tz (on ) Tj 0.991667 0 Td 52.391975 Tz (binary ) Tj 2.177778 0 Td 80.208333 Tz (QSAR ) Tj 2.216667 0 Td 46.990741 Tz (predictions. ) Tj 3.675 0 Td 58.333333 Tz (These ) Tj 2.041667 0 Td 61.574074 Tz (30 ) Tj 51.428571 0 0 51.428571 0 253.849315 Tm 6.358333 0 Td 52.777778 Tz (analogs ) Tj 2.488889 0 Td 59.143519 Tz (were ) Tj 1.691667 0 Td 49.608262 Tz (characterized ) Tj 4.122222 0 Td 50.231481 Tz (as ) Tj 0.855556 0 Td 77.777778 Tz (ATX ) Tj 1.691667 0 Td 46.018519 Tz (inhibitors ) Tj 3.033333 0 Td 53.148148 Tz (using ) Tj 1.847222 0 Td 48.611111 Tz (single ) Tj 51.428571 0 0 51.428571 0 216.27824 Tm 6.358333 0 Td 55.902778 Tz (dose ) Tj 1.477778 0 Td 49.583333 Tz (screening, ) Tj 3.111111 0 Td 49.016204 Tz (analysis ) Tj 2.527778 0 Td 55.092593 Tz (of ) Tj 0.738889 0 Td 44.781145 Tz (selectivity ) Tj 3.091667 0 Td 49.537037 Tz (against ) Tj 2.236111 0 Td 50.555556 Tz (other ) Tj 1.652778 0 Td 43.425926 Tz (lipid ) Tj 1.458333 0 Td 64.814815 Tz (pre ) Tj 51.428571 0 0 51.428571 0 170.331658 Tm 6.358333 0 Td 47.685185 Tz (ferring ) Tj 2.313889 0 Td 75.617284 Tz (NPP ) Tj 1.691667 0 Td 50.05144 Tz (isoforms, ) Tj 3.033333 0 Td 55.902778 Tz (dose ) Tj 1.711111 0 Td 52.256944 Tz (response ) Tj 2.858333 0 Td 49.475309 Tz (determinations, ) Tj 4.783333 0 Td 61.574074 Tz (and ) Tj 30 0 0 30 0 1091 Tm 41.566667 0 Td 80.555556 Tz (45 ) Tj 30 0 0 30 0 883 Tm 41.6 0 Td 80.555556 Tz (50 ) Tj 30 0 0 30 0 675 Tm 41.6 0 Td 77.777778 Tz (55 ) Tj 30 0 0 30 0 467 Tm 41.633333 0 Td 77.777778 Tz (60 ) Tj 30 0 0 30 0 259 Tm 41.633333 0 Td 75 Tz (65 ) Tj 52.857143 0 0 52.857143 0 2968 Tm 32.635135 0 Td 77.252252 Tz (26 ) Tj 51.428571 0 0 51.428571 0 2914.198502 Tm 25.297222 0 Td 60.853909 Tz (mechanism ) Tj 3.616667 0 Td 59.953704 Tz (of ) Tj 0.933333 0 Td 46.666667 Tz (inhibition ) Tj 3.130556 0 Td 48.611111 Tz (analysis ) Tj 2.683333 0 Td 48.611111 Tz (\(K, ) Tj 1.225 0 Td 49.04321 Tz (determination\). ) Tj 4.744444 0 Td 63.734568 Tz (The ) Tj 51.428571 0 0 51.428571 0 2876.103774 Tm 25.297222 0 Td 43.981481 Tz (fifteen ) Tj 1.983333 0 Td 52.314815 Tz (analogs ) Tj 2.352778 0 Td 45.37037 Tz (that ) Tj 1.186111 0 Td 47.890947 Tz (inhibited ) Tj 2.663889 0 Td 78.858025 Tz (ATX ) Tj 1.536111 0 Td 44.560185 Tz (activity ) Tj 2.294444 0 Td 79.398148 Tz (250% ) Tj 2.041667 0 Td 59.143519 Tz (were ) Tj 1.536111 0 Td 62.87037 Tz (shown ) Tj 51.428571 0 0 51.428571 0 2835.954198 Tm 25.277778 0 Td 45.37037 Tz (to ) Tj 0.777778 0 Td 59.953704 Tz (be ) Tj 0.875 0 Td 78.858025 Tz (ATX ) Tj 1.613889 0 Td 44.398148 Tz (selective. ) Tj 2.975 0 Td 51.203704 Tz (Eight ) Tj 1.730556 0 Td 52.314815 Tz (analogs ) Tj 2.411111 0 Td 50.411523 Tz (exhibited ) Tj 2.955556 0 Td 54.012346 Tz (ICs ) Tj 1.477778 0 Td 48.611111 Tz (for ) Tj 1.030556 0 Td 90.740741 Tz (ATX ) Tj 51.428571 0 0 51.428571 0 2796.661784 Tm 25.297222 0 Td 55.497685 Tz (mediated ) Tj 3.013889 0 Td 55.902778 Tz (FS-3 ) Tj 1.652778 0 Td 50.555556 Tz (hydrolysis ) Tj 3.344444 0 Td 44.560185 Tz (less ) Tj 1.4 0 Td 51.851852 Tz (than ) Tj 1.613889 0 Td 58.333333 Tz (10 ) Tj 1.030556 0 Td 61.574074 Tz (uM. ) Tj 1.458333 0 Td 51.851852 Tz (Five ) Tj 1.555556 0 Td 58.333333 Tz (of ) Tj 0.913889 0 Td 49.907407 Tz (these ) Tj 51.428571 0 0 51.428571 0 2759.813397 Tm 25.297222 0 Td 52.777778 Tz (analogs ) Tj 2.45 0 Td 50.411523 Tz (exhibited ) Tj 2.897222 0 Td 46.990741 Tz (either ) Tj 1.886111 0 Td 52.146465 Tz (competitive ) Tj 3.636111 0 Td 55.092593 Tz (or ) Tj 0.875 0 Td 52.849003 Tz (uncompetitive ) Tj 4.316667 0 Td 77.777778 Tz (ATX ) Tj 52.857143 0 0 52.857143 0 2716.227456 Tm 24.613514 0 Td 46.036036 Tz (inhibition ) Tj 3.027027 0 Td 51.238739 Tz (with ) Tj 1.551351 0 Td 52.027027 Tz (K, ) Tj 0.927027 0 Td 49.399399 Tz (values ) Tj 2.043243 0 Td 51.351351 Tz (ranging ) Tj 2.421622 0 Td 56.756757 Tz (from ) Tj 1.645946 0 Td 61.486486 Tz (30 ) Tj 1.002703 0 Td 78.828829 Tz (nM ) Tj 1.248649 0 Td 44.144144 Tz (to ) Tj 0.851351 0 Td 46.246246 Tz (1.5 ) Tj 1.154054 0 Td 60.960961 Tz (uM, ) Tj 51.428571 0 0 51.428571 0 2679.349068 Tm 25.277778 0 Td 59.62963 Tz (which ) Tj 2.002778 0 Td 58.333333 Tz (were ) Tj 1.652778 0 Td 45.37037 Tz (significantly ) Tj 3.772222 0 Td 46.450617 Tz (better ) Tj 1.886111 0 Td 51.851852 Tz (than ) Tj 1.438889 0 Td 55.092593 Tz (or ) Tj 0.836111 0 Td 50.231481 Tz (equivalent ) Tj 3.208333 0 Td 45.37037 Tz (to ) Tj 0.797222 0 Td 45.37037 Tz (that ) Tj 1.283333 0 Td 58.333333 Tz (of ) Tj 51.428571 0 0 51.428571 0 2640.272214 Tm 25.277778 0 Td 50.771605 Tz (the ) Tj 1.361111 0 Td 44.722222 Tz (lead. ) Tj 1.769444 0 Td 63.734568 Tz (The ) Tj 1.555556 0 Td 50.231481 Tz (best ) Tj 1.633333 0 Td 56.712963 Tz (of ) Tj 0.991667 0 Td 51.203704 Tz (these ) Tj 1.963889 0 Td 61.574074 Tz (compounds ) Tj 3.752778 0 Td 54.012346 Tz (has ) Tj 1.4 0 Td 58.333333 Tz (a ) Tj 0.738889 0 Td 55.092593 Tz (potency ) Tj 51.428571 0 0 51.428571 0 2600.770574 Tm 25.297222 0 Td 54.503367 Tz (approaching ) Tj 3.811111 0 Td 46.180556 Tz (that ) Tj 1.322222 0 Td 50.636574 Tz (reported ) Tj 2.644444 0 Td 48.611111 Tz (for ) Tj 1.069444 0 Td 64.814815 Tz (some ) Tj 1.788889 0 Td 56.712963 Tz (of ) Tj 0.797222 0 Td 50.771605 Tz (the ) Tj 1.147222 0 Td 58.333333 Tz (most ) Tj 1.613889 0 Td 47.530864 Tz (active ) Tj 1.944444 0 Td 73.45679 Tz (pub ) Tj 51.428571 0 0 51.428571 0 2560.417778 Tm 25.297222 0 Td 48.611111 Tz (lished ) Tj 1.944444 0 Td 44.074074 Tz (lipid-like ) Tj 2.780556 0 Td 78.858025 Tz (ATX ) Tj 1.594444 0 Td 44.486532 Tz (inhibitors. ) Tj 51.428571 0 0 51.428571 0 2520.558704 Tm 26.016667 0 Td 66.435185 Tz (AS ) Tj 1.088889 0 Td 49.259259 Tz (Such, ) Tj 1.769444 0 Td 50.771605 Tz (not ) Tj 1.166667 0 Td 52.662037 Tz (only ) Tj 1.555556 0 Td 56.712963 Tz (do ) Tj 0.952778 0 Td 64.00463 Tz (some ) Tj 1.788889 0 Td 56.712963 Tz (of ) Tj 0.836111 0 Td 50.555556 Tz (these ) Tj 1.75 0 Td 61.934156 Tz (compounds ) Tj 3.636111 0 Td 73.240741 Tz (demon ) Tj 51.428571 0 0 51.428571 0 2480.571788 Tm 25.316667 0 Td 43.209877 Tz (strate ) Tj 1.788889 0 Td 58.333333 Tz (a ) Tj 0.622222 0 Td 45.959596 Tz (significant ) Tj 3.266667 0 Td 56.944444 Tz (advance ) Tj 2.644444 0 Td 45.37037 Tz (in ) Tj 0.797222 0 Td 50.411523 Tz (autotaxin ) Tj 3.013889 0 Td 44.781145 Tz (inhibition, ) Tj 3.227778 0 Td 52.932099 Tz (but ) Tj 1.166667 0 Td 51.851852 Tz (the ) Tj 51.428571 0 0 51.428571 0 2442.332521 Tm 25.297222 0 Td 47.170782 Tz (potential ) Tj 2.761111 0 Td 48.611111 Tz (for ) Tj 1.069444 0 Td 47.685185 Tz (further ) Tj 2.197222 0 Td 56.983025 Tz (improvements ) Tj 4.336111 0 Td 45.37037 Tz (in ) Tj 0.758333 0 Td 77.777778 Tz (ATX ) Tj 1.594444 0 Td 46.990741 Tz (inhibition ) Tj 3.072222 0 Td 69.675926 Tz (meth ) Tj 51.428571 0 0 51.428571 0 2401.713598 Tm 25.297222 0 Td 55.092593 Tz (ods ) Tj 1.186111 0 Td 68.055556 Tz (may ) Tj 1.4 0 Td 58.333333 Tz (be ) Tj 0.836111 0 Td 48.251029 Tz (available ) Tj 2.780556 0 Td 53.240741 Tz (through ) Tj 2.430556 0 Td 48.611111 Tz (the ) Tj 1.05 0 Td 43.897306 Tz (utilization ) Tj 3.072222 0 Td 59.953704 Tz (of ) Tj 0.797222 0 Td 54.282407 Tz (combinations ) Tj 51.428571 0 0 51.428571 0 2361.680098 Tm 25.297222 0 Td 58.333333 Tz (of ) Tj 0.777778 0 Td 55.092593 Tz (Such ) Tj 1.497222 0 Td 61.934156 Tz (compounds ) Tj 3.538889 0 Td 48.611111 Tz (as ) Tj 0.797222 0 Td 51.041667 Tz (well ) Tj 1.4 0 Td 50.231481 Tz (as ) Tj 0.777778 0 Td 47.685185 Tz (further ) Tj 2.138889 0 Td 51.557239 Tz (refinements ) Tj 3.577778 0 Td 58.333333 Tz (and ) Tj 1.263889 0 Td 70.486111 Tz (modi ) Tj 51.428571 0 0 51.428571 0 2324.096447 Tm 25.297222 0 Td 45.37037 Tz (fications ) Tj 2.838889 0 Td 58.333333 Tz (of ) Tj 0.972222 0 Td 46.759259 Tz (certain ) Tj 2.352778 0 Td 50.771605 Tz (intermediate ) Tj 4.025 0 Td 61.574074 Tz (compounds ) Tj 3.694444 0 Td 51.851852 Tz (as ) Tj 0.991667 0 Td 54.282407 Tz (provided ) Tj 40 0 0 40 0 2289 Tm 32.525 0 Td 66.666667 Tz (above. ) Tj 51.428571 0 0 51.428571 0 2243.548718 Tm 25.297222 0 Td 48.611111 Tz (Effects ) Tj 2.352778 0 Td 56.712963 Tz (of ) Tj 0.894444 0 Td 54.372428 Tz (Pipemidic ) Tj 3.227778 0 Td 58.333333 Tz (Acid ) Tj 1.672222 0 Td 77.777778 Tz (ATX ) Tj 1.730556 0 Td 46.342593 Tz (Inhibitors ) Tj 3.111111 0 Td 59.953704 Tz (on ) Tj 0.972222 0 Td 66.759259 Tz (A2058 ) Tj 2.294444 0 Td 50.231481 Tz (Cell ) Tj 51.428571 0 0 51.428571 0 2210 Tm 25.297222 0 Td 54.372428 Tz (Migration ) Tj 51.428571 0 0 51.428571 0 2165.039216 Tm 26.016667 0 Td 66.111111 Tz (A2058 ) Tj 2.158333 0 Td 44.722222 Tz (cells ) Tj 1.555556 0 Td 59.953704 Tz (were ) Tj 1.613889 0 Td 55.092593 Tz (seeded ) Tj 2.177778 0 Td 46.990741 Tz (in ) Tj 0.777778 0 Td 52.314815 Tz (96-well ) Tj 2.391667 0 Td 47.530864 Tz (plates ) Tj 1.905556 0 Td 45.37037 Tz (at ) Tj 0.738889 0 Td 51.851852 Tz (a ) Tj 0.525 0 Td 49.537037 Tz (density ) Tj 2.275 0 Td 59.953704 Tz (of ) Tj 51.428571 0 0 51.428571 0 2129.857143 Tm 25.316667 0 Td 55.632716 Tz (50,000 ) Tj 2.158333 0 Td 44.074074 Tz (cells ) Tj 1.497222 0 Td 54.012346 Tz (per ) Tj 1.127778 0 Td 51.041667 Tz (well ) Tj 1.419444 0 Td 43.75 Tz (in ) Tj 0.7 0 Td 56.30787 Tz (complete ) Tj 2.858333 0 Td 57.253086 Tz (growth ) Tj 2.236111 0 Td 65.354938 Tz (medium ) Tj 2.547222 0 Td 80.478395 Tz (\(DMEM+ ) Tj 51.428571 0 0 51.428571 0 2096.043628 Tm 25.375 0 Td 68.055556 Tz (10% ) Tj 1.419444 0 Td 49.59087 Tz (FBS--penicillin/streptomycin--L-glutamine\). ) Tj 12.911111 0 Td 50.555556 Tz (Cells ) Tj 1.672222 0 Td 58.333333 Tz (were ) Tj 51.428571 0 0 51.428571 0 2055.645244 Tm 25.297222 0 Td 54.166667 Tz (allowed ) Tj 2.508333 0 Td 45.37037 Tz (to ) Tj 0.777778 0 Td 47.138047 Tz (equilibrate ) Tj 3.325 0 Td 48.611111 Tz (for ) Tj 1.05 0 Td 61.574074 Tz (24 ) Tj 0.933333 0 Td 53.796296 Tz (hours ) Tj 1.847222 0 Td 45.37037 Tz (at ) Tj 0.719444 0 Td 56.17284 Tz (37 ) Tj 1.244444 0 Td 55.092593 Tz (C. ) Tj 0.875 0 Td 54.282407 Tz (with ) Tj 1.516667 0 Td 81.018519 Tz (5% ) Tj 1.166667 0 Td 82.098765 Tz (CO. ) Tj 51.428571 0 0 51.428571 0 2020.435233 Tm 25.297222 0 Td 49.259259 Tz (Cells ) Tj 1.808333 0 Td 58.333333 Tz (were ) Tj 1.711111 0 Td 50.231481 Tz (then ) Tj 1.516667 0 Td 54.398148 Tz (serum-deprived ) Tj 4.861111 0 Td 47.530864 Tz (for ) Tj 1.108333 0 Td 59.953704 Tz (24 ) Tj 1.011111 0 Td 53.796296 Tz (hours ) Tj 1.944444 0 Td 43.75 Tz (in ) Tj 0.855556 0 Td 88.148148 Tz (DMEM+ ) Tj 51.428571 0 0 51.428571 0 1988.160479 Tm 25.297222 0 Td 62.384259 Tz (0.1% ) Tj 2.138889 0 Td 52.094907 Tz (BSA+penicillin/streptomycin--L-glutamine ) Tj 13.086111 0 Td 62.114198 Tz (\(serum ) Tj 51.428571 0 0 51.428571 0 1947.594096 Tm 25.297222 0 Td 46.990741 Tz (free ) Tj 1.361111 0 Td 57.523148 Tz (medium\). ) Tj 2.955556 0 Td 51.851852 Tz (After ) Tj 1.75 0 Td 58.333333 Tz (24 ) Tj 0.913889 0 Td 49.691358 Tz (hours, ) Tj 2.002778 0 Td 49.691358 Tz (the ) Tj 1.108333 0 Td 58.333333 Tz (monolayer ) Tj 3.305556 0 Td 60.493827 Tz (was ) Tj 1.341667 0 Td 50.771605 Tz (scratched ) Tj 51.428571 0 0 51.428571 0 1912.392811 Tm 25.277778 0 Td 53.148148 Tz (using ) Tj 1.788889 0 Td 58.333333 Tz (a ) Tj 0.544444 0 Td 42.592593 Tz (sterile ) Tj 2.002778 0 Td 59.41358 Tz (200 ) Tj 1.322222 0 Td 40.509259 Tz (ul ) Tj 0.719444 0 Td 47.222222 Tz (pipette ) Tj 2.177778 0 Td 39.699074 Tz (tip, ) Tj 1.147222 0 Td 59.41358 Tz (and ) Tj 1.263889 0 Td 55.902778 Tz (each ) Tj 1.555556 0 Td 51.851852 Tz (well ) Tj 1.477778 0 Td 60.493827 Tz (was ) Tj 1.322222 0 Td 60.493827 Tz (washed ) Tj 51.428571 0 0 51.428571 0 1874.341554 Tm 25.277778 0 Td 54.282407 Tz (with ) Tj 1.516667 0 Td 59.953704 Tz (50 ) Tj 0.933333 0 Td 42.12963 Tz (ul ) Tj 0.7 0 Td 52.5 Tz (serum-free ) Tj 3.363889 0 Td 64.274691 Tz (medium ) Tj 2.547222 0 Td 45.37037 Tz (to ) Tj 0.738889 0 Td 59.41358 Tz (remove ) Tj 2.313889 0 Td 62.962963 Tz (damaged ) Tj 2.8 0 Td 44.722222 Tz (cells ) Tj 1.497222 0 Td 61.574074 Tz (and ) Tj 51.428571 0 0 51.428571 0 1837 Tm 25.277778 0 Td 48.148148 Tz (treated ) Tj 2.138889 0 Td 52.662037 Tz (with ) Tj 1.438889 0 Td 72.376543 Tz (LPA ) Tj 1.497222 0 Td 47.800926 Tz (18:1 ) Tj 1.361111 0 Td 52.932099 Tz (\(10 ) Tj 1.127778 0 Td 56.712963 Tz (uM\), ) Tj 1.555556 0 Td 72.376543 Tz (LPC ) Tj 1.516667 0 Td 46.990741 Tz (18:1 ) Tj 1.341667 0 Td 55.092593 Tz (\(10 ) Tj 1.147222 0 Td 57.523148 Tz (uM\), ) Tj 1.497222 0 Td 77.777778 Tz (ATX ) Tj 1.555556 0 Td 54.282407 Tz (\(100 ) Tj 51.428571 0 0 51.428571 0 1802.869732 Tm 25.297222 0 Td 50 Tz (ng/ml\), ) Tj 2.294444 0 Td 55.092593 Tz (or ) Tj 0.816667 0 Td 55.092593 Tz (a ) Tj 0.544444 0 Td 54.79798 Tz (combination ) Tj 3.830556 0 Td 59.953704 Tz (of ) Tj 0.836111 0 Td 72.376543 Tz (LPC ) Tj 1.575 0 Td 47.800926 Tz (18:1 ) Tj 1.4 0 Td 60.493827 Tz (and ) Tj 1.263889 0 Td 76.697531 Tz (ATX ) Tj 1.594444 0 Td 45.37037 Tz (in ) Tj 0.777778 0 Td 48.611111 Tz (the ) Tj 1.069444 0 Td 60.763889 Tz (pres ) Tj 51.428571 0 0 51.428571 0 1766.444848 Tm 25.297222 0 Td 55.902778 Tz (ence ) Tj 1.497222 0 Td 58.333333 Tz (and ) Tj 1.205556 0 Td 55.092593 Tz (absence ) Tj 2.469444 0 Td 58.333333 Tz (of ) Tj 0.777778 0 Td 53.652263 Tz (pipemidic ) Tj 3.052778 0 Td 51.851852 Tz (acid ) Tj 1.380556 0 Td 77.777778 Tz (ATX ) Tj 1.575 0 Td 46.018519 Tz (inhibitors ) Tj 2.955556 0 Td 52.932099 Tz (\(30 ) Tj 1.147222 0 Td 57.523148 Tz (uM\). ) Tj 52.857143 0 0 52.857143 0 1728.877928 Tm 24.613514 0 Td 62.012012 Tz (The ) Tj 1.22973 0 Td 53.603604 Tz (width ) Tj 1.778378 0 Td 53.603604 Tz (of ) Tj 0.718919 0 Td 48.348348 Tz (the ) Tj 1.002703 0 Td 46.771772 Tz (injury ) Tj 1.816216 0 Td 60.960961 Tz (was ) Tj 1.248649 0 Td 57.150901 Tz (measured ) Tj 2.837838 0 Td 45.720721 Tz (at ) Tj 0.662162 0 Td 43.093093 Tz (To. ) Tj 1.021622 0 Td 56.756757 Tz (4 ) Tj 0.472973 0 Td 53.603604 Tz (hours ) Tj 1.759459 0 Td 46.036036 Tz (\(data ) Tj 1.532432 0 Td 51.501502 Tz (not ) Tj 51.428571 0 0 51.428571 0 1693 Tm 25.316667 0 Td 54.166667 Tz (shown\), ) Tj 2.566667 0 Td 61.574074 Tz (24 ) Tj 1.011111 0 Td 53.796296 Tz (hours ) Tj 1.925 0 Td 47.962963 Tz (\(data ) Tj 1.75 0 Td 51.851852 Tz (not ) Tj 1.225 0 Td 54.166667 Tz (shown\), ) Tj 2.586111 0 Td 58.333333 Tz (and ) Tj 1.322222 0 Td 59.953704 Tz (48 ) Tj 1.030556 0 Td 53.148148 Tz (hours ) Tj 1.925 0 Td 58.873457 Tz (\(shown ) Tj 51.428571 0 0 51.428571 0 1660.522167 Tm 25.297222 0 Td 54.552469 Tz (above\) ) Tj 2.158333 0 Td 46.018519 Tz (after ) Tj 1.575 0 Td 49.016204 Tz (injury/treatment ) Tj 4.9 0 Td 52.5 Tz (using ) Tj 1.827778 0 Td 47.530864 Tz (the ) Tj 1.166667 0 Td 57.253086 Tz (10x ) Tj 1.263889 0 Td 48.971193 Tz (objective ) Tj 2.858333 0 Td 59.953704 Tz (of ) Tj 0.816667 0 Td 50.771605 Tz (the ) Tj 52.857143 0 0 52.857143 0 1622.89 Tm 24.613514 0 Td 48.873874 Tz (phase-contrast ) Tj 4.408108 0 Td 54.234234 Tz (microscope ) Tj 3.537838 0 Td 57.807808 Tz (and ) Tj 1.362162 0 Td 48.348348 Tz (the ) Tj 1.191892 0 Td 57.282282 Tz (Micron ) Tj 2.364865 0 Td 75.675676 Tz (USB ) Tj 1.702703 0 Td 50.844595 Tz (software ) Tj 51.428571 0 0 51.428571 0 1586.749077 Tm 25.297222 0 Td 53.06713 Tz (package. ) Tj 2.8 0 Td 56.712963 Tz (Data ) Tj 1.575 0 Td 49.691358 Tz (represent ) Tj 2.916667 0 Td 64.00463 Tz (mean ) Tj 1.75 0 Td 51.851852 Tz (percent ) Tj 2.391667 0 Td 54.208754 Tz (closuretSD. ) Tj 3.869444 0 Td 59.41358 Tz (n=3 ) Tj 1.341667 0 Td 47.530864 Tz (for ) Tj 51.428571 0 0 51.428571 0 1551.120894 Tm 25.297222 0 Td 55.092593 Tz (each ) Tj 1.769444 0 Td 52.146465 Tz (experiment. ) Tj 3.927778 0 Td 56.712963 Tz (Data ) Tj 1.808333 0 Td 59.143519 Tz (were ) Tj 1.847222 0 Td 54.6875 Tz (analyzed ) Tj 3.091667 0 Td 51.851852 Tz (using ) Tj 1.983333 0 Td 51.203704 Tz (two-factor ) Tj 51.428571 0 0 51.428571 0 1512.957041 Tm 25.297222 0 Td 82.962963 Tz (ANOVA ) Tj 2.644444 0 Td 53.472222 Tz (with ) Tj 1.497222 0 Td 50.771605 Tz (Bonferronis ) Tj 3.811111 0 Td 45.730453 Tz (post-test ) Tj 2.605556 0 Td 46.990741 Tz (to ) Tj 0.738889 0 Td 53.652263 Tz (determine ) Tj 3.033333 0 Td 43.75 Tz (if ) Tj 0.602778 0 Td 49.691358 Tz (the ) Tj 1.011111 0 Td 63.194444 Tz (pipe ) Tj 51.428571 0 0 51.428571 0 1478.088548 Tm 25.297222 0 Td 55.092593 Tz (midic ) Tj 1.769444 0 Td 51.041667 Tz (acid ) Tj 1.341667 0 Td 46.666667 Tz (inhibitors ) Tj 2.936111 0 Td 45.868946 Tz (significantly ) Tj 3.733333 0 Td 54.62963 Tz (reduced ) Tj 2.411111 0 Td 42.939815 Tz (cell ) Tj 1.205556 0 Td 51.49177 Tz (migration ) Tj 2.955556 0 Td 61.574074 Tz (ver ) Tj 51.428571 0 0 51.428571 0 1441.194103 Tm 25.316667 0 Td 48.611111 Tz (sus ) Tj 1.127778 0 Td 49.537037 Tz (vehicle ) Tj 2.294444 0 Td 46.180556 Tz (control. ) Tj 2.488889 0 Td 55.452675 Tz (*=p-0.05; ) Tj 3.247222 0 Td 55.416667 Tz (**=p<0.01. ) Tj 3.519444 0 Td 57.685185 Tz (These ) Tj 1.963889 0 Td 51.041667 Tz (data ) Tj 1.419444 0 Td 57.523148 Tz (indi ) Tj 51.428571 0 0 51.428571 0 1403.782082 Tm 25.297222 0 Td 49.421296 Tz (cate ) Tj 1.341667 0 Td 45.37037 Tz (that ) Tj 1.302778 0 Td 38.888889 Tz (1 ) Tj 0.466667 0 Td 45.868946 Tz (significantly ) Tj 3.772222 0 Td 47.890947 Tz (inhibited ) Tj 2.722222 0 Td 54.282407 Tz (both ) Tj 1.438889 0 Td 69.675926 Tz (ATX- ) Tj 1.808333 0 Td 59.41358 Tz (and ) Tj 1.263889 0 Td 79.62963 Tz (LPC+ATX ) Tj 51.428571 0 0 51.428571 0 1367.636364 Tm 25.316667 0 Td 50.231481 Tz (stimulated ) Tj 3.558333 0 Td 51.851852 Tz (migration ) Tj 3.344444 0 Td 45.37037 Tz (in ) Tj 1.069444 0 Td 65.462963 Tz (A2058 ) Tj 2.508333 0 Td 41.589506 Tz (cells, ) Tj 2.041667 0 Td 45.37037 Tz (after ) Tj 1.866667 0 Td 59.953704 Tz (48 ) Tj 1.244444 0 Td 49.691358 Tz (hours. ) Tj 51.428571 0 0 51.428571 0 1333.467363 Tm 25.297222 0 Td 48.860399 Tz (Additionally, ) Tj 4.277778 0 Td 32.407407 Tz (1 ) Tj 0.680556 0 Td 55.092593 Tz (appeared ) Tj 3.033333 0 Td 45.37037 Tz (to ) Tj 0.933333 0 Td 49.421296 Tz (also ) Tj 1.613889 0 Td 53.472222 Tz (reduce ) Tj 2.352778 0 Td 54.62963 Tz (LPC-stimulated ) Tj 51.428571 0 0 51.428571 0 1299.273585 Tm 25.297222 0 Td 49.583333 Tz (migration, ) Tj 3.111111 0 Td 53.06713 Tz (although ) Tj 2.683333 0 Td 48.611111 Tz (the ) Tj 1.030556 0 Td 50.411523 Tz (reduction ) Tj 2.858333 0 Td 61.574074 Tz (was ) Tj 1.263889 0 Td 50.771605 Tz (not ) Tj 1.030556 0 Td 42.12963 Tz (statistically ) Tj 3.422222 0 Td 49.074074 Tz (signifi ) Tj 51.428571 0 0 51.428571 0 1259.390863 Tm 25.297222 0 Td 44.722222 Tz (cant. ) Tj 1.613889 0 Td 61.574074 Tz (20 ) Tj 0.933333 0 Td 58.333333 Tz (and ) Tj 1.322222 0 Td 53.472222 Tz (14 ) Tj 0.836111 0 Td 49.421296 Tz (also ) Tj 1.380556 0 Td 55.497685 Tz (appeared ) Tj 2.858333 0 Td 46.990741 Tz (to ) Tj 0.797222 0 Td 51.851852 Tz (decrease ) Tj 2.722222 0 Td 57.685185 Tz (LPC-, ) Tj 1.905556 0 Td 60.925926 Tz (ATX-, ) Tj 2.022222 0 Td 60.493827 Tz (and ) Tj 51.428571 0 0 51.428571 0 1222.509248 Tm 25.316667 0 Td 63.08642 Tz (LPC+ATX-induced ) Tj 5.969444 0 Td 43.75 Tz (cell ) Tj 1.4 0 Td 49.583333 Tz (migration. ) Tj 3.344444 0 Td 57.118056 Tz (However, ) Tj 3.072222 0 Td 49.907407 Tz (these ) Tj 1.827778 0 Td 60.925926 Tz (reduc ) Tj 51.428571 0 0 51.428571 0 1189.567521 Tm 25.277778 0 Td 47.314815 Tz (tions ) Tj 1.633333 0 Td 57.523148 Tz (were ) Tj 1.575 0 Td 48.611111 Tz (also ) Tj 1.380556 0 Td 50.771605 Tz (not ) Tj 1.088889 0 Td 42.378917 Tz (statistically ) Tj 3.5 0 Td 44.290123 Tz (significant. ) Tj 51.428571 0 0 51.428571 0 1154.051546 Tm 26.016667 0 Td 54.444444 Tz (Thus, ) Tj 1.886111 0 Td 67.24537 Tz (Compound ) Tj 3.519444 0 Td 35.648148 Tz (1 ) Tj 0.544444 0 Td 59.62963 Tz (shows ) Tj 2.061111 0 Td 41.880342 Tz (statistically ) Tj 3.519444 0 Td 45.959596 Tz (significant ) Tj 3.286111 0 Td 53.472222 Tz (inhibi ) Tj 51.428571 0 0 51.428571 0 1111.737033 Tm 25.277778 0 Td 46.990741 Tz (tion ) Tj 1.341667 0 Td 58.333333 Tz (of ) Tj 0.797222 0 Td 42.939815 Tz (cell ) Tj 1.263889 0 Td 51.49177 Tz (migration ) Tj 3.013889 0 Td 49.907407 Tz (stimulated ) Tj 3.188889 0 Td 59.953704 Tz (by ) Tj 0.894444 0 Td 69.907407 Tz (ATX/LPC ) Tj 3.130556 0 Td 49.109687 Tz (co-treatment. ) Tj 51.428571 0 0 51.428571 0 1071.212435 Tm 25.297222 0 Td 53.472222 Tz (This ) Tj 1.613889 0 Td 49.421296 Tz (data ) Tj 1.497222 0 Td 53.914141 Tz (demonstrate ) Tj 3.869444 0 Td 45.37037 Tz (that ) Tj 1.361111 0 Td 49.691358 Tz (the ) Tj 1.205556 0 Td 45.37037 Tz (in ) Tj 0.875 0 Td 44.722222 Tz (vitro ) Tj 1.652778 0 Td 63.194444 Tz (enzyme ) Tj 2.566667 0 Td 47.314815 Tz (inhibition ) Tj 51.428571 0 0 51.428571 0 1033.387016 Tm 25.297222 0 Td 54.6875 Tz (observed ) Tj 2.858333 0 Td 48.611111 Tz (for ) Tj 1.069444 0 Td 43.75 Tz (this ) Tj 1.302778 0 Td 64.00463 Tz (compound ) Tj 3.305556 0 Td 45.694444 Tz (translates ) Tj 2.994444 0 Td 46.990741 Tz (into ) Tj 1.380556 0 Td 55.092593 Tz (a ) Tj 0.583333 0 Td 45.37037 Tz (cellular ) Tj 2.391667 0 Td 52.5 Tz (assay ) Tj 51.428571 0 0 51.428571 0 992.970732 Tm 25.316667 0 Td 54.552469 Tz (system ) Tj 2.197222 0 Td 47.800926 Tz (relevant ) Tj 2.45 0 Td 48.611111 Tz (to ) Tj 0.797222 0 Td 47.43266 Tz (metastasis. ) Tj 51.428571 0 0 51.428571 0 952.842105 Tm 26.016667 0 Td 57.685185 Tz (There ) Tj 1.944444 0 Td 43.75 Tz (are, ) Tj 1.322222 0 Td 56.712963 Tz (of ) Tj 0.836111 0 Td 48.611111 Tz (course, ) Tj 2.333333 0 Td 66.435185 Tz (many ) Tj 1.827778 0 Td 45.959596 Tz (alternative ) Tj 3.247222 0 Td 59.511785 Tz (embodiments ) Tj 4.161111 0 Td 60.493827 Tz (and ) Tj 51.428571 0 0 51.428571 0 913.043478 Tm 25.297222 0 Td 50.605413 Tz (modifications ) Tj 4.141667 0 Td 59.953704 Tz (of ) Tj 0.797222 0 Td 49.691358 Tz (the ) Tj 1.069444 0 Td 50 Tz (present ) Tj 2.275 0 Td 50.411523 Tz (invention ) Tj 2.897222 0 Td 58.981481 Tz (which ) Tj 1.963889 0 Td 49.691358 Tz (are ) Tj 1.069444 0 Td 52.256944 Tz (intended ) Tj 2.683333 0 Td 45.37037 Tz (to ) Tj 51.428571 0 0 51.428571 0 874.694737 Tm 25.277778 0 Td 61.574074 Tz (be ) Tj 0.894444 0 Td 52.256944 Tz (included ) Tj 2.683333 0 Td 51.311728 Tz (within ) Tj 2.041667 0 Td 49.691358 Tz (the ) Tj 1.088889 0 Td 41.049383 Tz (spirit ) Tj 1.633333 0 Td 59.41358 Tz (and ) Tj 1.263889 0 Td 55.092593 Tz (scope ) Tj 1.827778 0 Td 59.953704 Tz (of ) Tj 0.797222 0 Td 42.939815 Tz (this ) Tj 1.244444 0 Td 47.314815 Tz (invention. ) Tj 40 0 0 40 0 841 Tm 33.45 0 Td 85.416667 Tz (What ) Tj 2.275 0 Td 91.666667 Tz (we ) Tj 1.3 0 Td 69.166667 Tz (claim ) Tj 2.325 0 Td 45.833333 Tz (is: ) Tj 51.428571 0 0 51.428571 0 799.223594 Tm 26.036111 0 Td 42.12963 Tz (1. ) Tj 0.680556 0 Td 87.5 Tz (A ) Tj 0.719444 0 Td 63.599537 Tz (compound ) Tj 3.227778 0 Td 56.712963 Tz (conforming ) Tj 3.577778 0 Td 46.990741 Tz (to ) Tj 0.758333 0 Td 48.611111 Tz (the ) Tj 1.088889 0 Td 51.851852 Tz (following ) Tj 2.975 0 Td 51.041667 Tz (formula: ) Tj 31.428571 0 0 31.428571 0 622 Tm 41.681818 0 Td 106.060606 Tz (HOOC ) Tj 1.428571 0 0 1.428571 0 708 Tm 974.4 0 Td 116.666667 Tz ( ) Tj ET Q endstream endobj 302 0 obj << /Length 1 >> stream q endstream endobj 303 0 obj << /Length 15159 >> stream Q q 0.24 0 0 0.24 0 0 cm BT /F1 1 Tf 3 Tr 62.857143 0 0 62.857143 0 3023 Tm 17.325 0 Td 83.522727 Tz (US ) Tj 1.240909 0 Td 57.154882 Tz (8,497,371 ) Tj 3.388636 0 Td 74.242424 Tz (B2 ) Tj 52.857143 0 0 52.857143 0 2968 Tm 14.208108 0 Td 78.828829 Tz (27 ) Tj 51.428571 0 0 51.428571 0 2915.252632 Tm 7.077778 0 Td 55.555556 Tz (wherein ) Tj 2.547222 0 Td 56.712963 Tz (Rs ) Tj 0.913889 0 Td 37.268519 Tz (is ) Tj 0.602778 0 Td 54.372428 Tz (hydrogen; ) Tj 3.15 0 Td 54.62963 Tz (wherein ) Tj 2.527778 0 Td 74.537037 Tz (R ) Tj 0.894444 0 Td 68.055556 Tz (may ) Tj 1.361111 0 Td 59.953704 Tz (be ) Tj 0.894444 0 Td 48.611111 Tz (selected ) Tj 2.488889 0 Td 56.712963 Tz (indi ) Tj 51.428571 0 0 51.428571 0 2875.640449 Tm 7.816667 0 Td 49.421296 Tz (vidually ) Tj 2.722222 0 Td 57.523148 Tz (from ) Tj 1.711111 0 Td 50.771605 Tz (the ) Tj 1.205556 0 Td 57.037037 Tz (group ) Tj 2.061111 0 Td 48.935185 Tz (consisting ) Tj 3.266667 0 Td 56.712963 Tz (of ) Tj 0.913889 0 Td 57.118056 Tz (hydrogen ) Tj 3.052778 0 Td 61.574074 Tz (and ) Tj 51.428571 0 0 51.428571 0 2829.589603 Tm 7.816667 0 Td 48.611111 Tz (chloro; ) Tj 2.294444 0 Td 74.537037 Tz (R ) Tj 0.913889 0 Td 66.975309 Tz (may ) Tj 1.4 0 Td 59.953704 Tz (be ) Tj 0.855556 0 Td 49.016204 Tz (selected ) Tj 2.527778 0 Td 48.341049 Tz (individually ) Tj 3.675 0 Td 57.523148 Tz (from ) Tj 1.575 0 Td 49.691358 Tz (the ) Tj 1.069444 0 Td 56.388889 Tz (group ) Tj 51.428571 0 0 51.428571 0 2789.042913 Tm 7.816667 0 Td 49.259259 Tz (consisting ) Tj 3.130556 0 Td 58.333333 Tz (of ) Tj 0.777778 0 Td 54.372428 Tz (hydrogen, ) Tj 3.111111 0 Td 51.851852 Tz (halogen, ) Tj 2.722222 0 Td 51.388889 Tz (methyl, ) Tj 2.391667 0 Td 54.6875 Tz (methoxy, ) Tj 2.8 0 Td 60.493827 Tz (and ) Tj 52.857143 0 0 52.857143 0 2743.245542 Tm 7.586486 0 Td 46.509009 Tz (trifluoromethyl; ) Tj 4.748649 0 Td 75.675676 Tz (R ) Tj 0.983784 0 Td 66.216216 Tz (may ) Tj 1.437838 0 Td 55.18018 Tz (be ) Tj 0.908108 0 Td 47.297297 Tz (selected ) Tj 2.516216 0 Td 47.034535 Tz (individually ) Tj 3.651351 0 Td 56.756757 Tz (from ) Tj 51.428571 0 0 51.428571 0 2700.413299 Tm 7.797222 0 Td 50.771605 Tz (the ) Tj 1.108333 0 Td 56.388889 Tz (group ) Tj 1.925 0 Td 49.259259 Tz (consisting ) Tj 3.15 0 Td 58.333333 Tz (of ) Tj 0.797222 0 Td 54.372428 Tz (hydrogen, ) Tj 3.130556 0 Td 52.256944 Tz (halogen, ) Tj 2.702778 0 Td 53.472222 Tz (trifluorom ) Tj 51.428571 0 0 51.428571 0 2655.716016 Tm 7.816667 0 Td 45.37037 Tz (ethyl, ) Tj 1.769444 0 Td 59.41358 Tz (and ) Tj 1.225 0 Td 51.851852 Tz (methyl; ) Tj 2.372222 0 Td 77.777778 Tz (R ) Tj 0.894444 0 Td 68.055556 Tz (may ) Tj 1.380556 0 Td 55.092593 Tz (be ) Tj 0.836111 0 Td 48.611111 Tz (selected ) Tj 2.488889 0 Td 48.341049 Tz (individually ) Tj 3.655556 0 Td 58.333333 Tz (from ) Tj 51.428571 0 0 51.428571 0 2613.372654 Tm 7.797222 0 Td 50.771605 Tz (the ) Tj 1.147222 0 Td 55.740741 Tz (group ) Tj 1.925 0 Td 49.259259 Tz (consisting ) Tj 3.188889 0 Td 59.953704 Tz (of ) Tj 0.816667 0 Td 54.372428 Tz (hydrogen, ) Tj 3.208333 0 Td 48.148148 Tz (chloro, ) Tj 2.275 0 Td 51.851852 Tz (methyl, ) Tj 2.391667 0 Td 61.574074 Tz (and ) Tj 51.428571 0 0 51.428571 0 2567.480292 Tm 7.797222 0 Td 47.800926 Tz (trifluoromethyl; ) Tj 4.861111 0 Td 59.41358 Tz (and ) Tj 1.302778 0 Td 55.555556 Tz (wherein ) Tj 2.644444 0 Td 74.537037 Tz (R ) Tj 0.972222 0 Td 58.333333 Tz (and ) Tj 1.361111 0 Td 71.296296 Tz (R ) Tj 0.991667 0 Td 66.975309 Tz (may ) Tj 1.438889 0 Td 59.953704 Tz (be ) Tj 0.972222 0 Td 82.098765 Tz (com ) Tj 51.428571 0 0 51.428571 0 2521.057851 Tm 7.797222 0 Td 54.444444 Tz (bined ) Tj 1.769444 0 Td 48.611111 Tz (to ) Tj 0.758333 0 Td 57.523148 Tz (form ) Tj 1.555556 0 Td 58.333333 Tz (a ) Tj 0.505556 0 Td 48.316498 Tz (thiadiazole ) Tj 3.344444 0 Td 51.851852 Tz (group, ) Tj 2.061111 0 Td 43.75 Tz (in ) Tj 0.7 0 Td 58.981481 Tz (which ) Tj 1.963889 0 Td 51.851852 Tz (case ) Tj 1.438889 0 Td 77.777778 Tz (R ) Tj 0.855556 0 Td 61.574074 Tz (and ) Tj 52.857143 0 0 52.857143 0 2477.680672 Tm 7.624324 0 Td 72.522523 Tz (Rare ) Tj 1.891892 0 Td 52.552553 Tz (hydrogen; ) Tj 3.008108 0 Td 54.054054 Tz (wherein ) Tj 2.421622 0 Td 42.567568 Tz (if ) Tj 0.624324 0 Td 75.675676 Tz (R ) Tj 0.87027 0 Td 36.261261 Tz (is ) Tj 0.605405 0 Td 46.846847 Tz (chloro, ) Tj 2.1 0 Td 51.238739 Tz (then ) Tj 1.437838 0 Td 72.522523 Tz (R ) Tj 0.832432 0 Td 39.414414 Tz (is ) Tj 0.605405 0 Td 48.085586 Tz (also ) Tj 51.428571 0 0 51.428571 0 2434.824773 Tm 7.816667 0 Td 48.611111 Tz (chloro, ) Tj 2.255556 0 Td 60.493827 Tz (and ) Tj 1.361111 0 Td 53.472222 Tz (R2 ) Tj 0.972222 0 Td 58.333333 Tz (and ) Tj 1.341667 0 Td 74.537037 Tz (R ) Tj 0.972222 0 Td 49.691358 Tz (are ) Tj 1.108333 0 Td 54.372428 Tz (hydrogen; ) Tj 3.208333 0 Td 55.555556 Tz (wherein ) Tj 2.605556 0 Td 43.75 Tz (if ) Tj 0.719444 0 Td 74.537037 Tz (R ) Tj 0.991667 0 Td 38.888889 Tz (is ) Tj 51.428571 0 0 51.428571 0 2393.484848 Tm 7.797222 0 Td 55.092593 Tz (halogen ) Tj 2.508333 0 Td 51.851852 Tz (or ) Tj 0.797222 0 Td 55.497685 Tz (methoxy, ) Tj 2.838889 0 Td 51.851852 Tz (then ) Tj 1.497222 0 Td 71.296296 Tz (R. ) Tj 1.127778 0 Td 71.296296 Tz (R. ) Tj 1.069444 0 Td 58.333333 Tz (and ) Tj 1.283333 0 Td 55.092593 Tz (Ra ) Tj 0.875 0 Td 50.771605 Tz (are ) Tj 1.069444 0 Td 54.372428 Tz (hydrogen; ) Tj 52.857143 0 0 52.857143 0 2348.786517 Tm 7.586486 0 Td 54.954955 Tz (wherein ) Tj 2.478378 0 Td 44.144144 Tz (if ) Tj 0.643243 0 Td 75.675676 Tz (R ) Tj 0.908108 0 Td 37.837838 Tz (is ) Tj 0.662162 0 Td 47.297297 Tz (trifluoromethyl ) Tj 4.445946 0 Td 52.027027 Tz (or ) Tj 0.794595 0 Td 50.45045 Tz (methyl, ) Tj 2.308108 0 Td 50.45045 Tz (then ) Tj 1.437838 0 Td 75.675676 Tz (R ) Tj 0.889189 0 Td 58.858859 Tz (and ) Tj 51.428571 0 0 51.428571 0 2305.040431 Tm 7.836111 0 Td 56.712963 Tz (Rs ) Tj 0.875 0 Td 49.691358 Tz (are ) Tj 0.991667 0 Td 57.118056 Tz (hydrogen ) Tj 2.877778 0 Td 58.333333 Tz (and ) Tj 1.205556 0 Td 81.018519 Tz (R ) Tj 0.836111 0 Td 40.509259 Tz (is ) Tj 0.602778 0 Td 46.990741 Tz (either ) Tj 1.769444 0 Td 57.118056 Tz (hydrogen ) Tj 2.877778 0 Td 53.472222 Tz (or ) Tj 0.719444 0 Td 49.691358 Tz (the ) Tj 1.011111 0 Td 62.384259 Tz (same ) Tj 1.594444 0 Td 51.851852 Tz (as ) Tj 51.428571 0 0 51.428571 0 2263.071332 Tm 7.836111 0 Td 76.157407 Tz (R; ) Tj 1.108333 0 Td 55.092593 Tz (wherein ) Tj 2.469444 0 Td 43.75 Tz (if ) Tj 0.602778 0 Td 77.777778 Tz (R ) Tj 0.913889 0 Td 37.268519 Tz (is ) Tj 0.602778 0 Td 51.446759 Tz (halogen, ) Tj 2.625 0 Td 47.395833 Tz (trifluoromethyl, ) Tj 4.725 0 Td 51.851852 Tz (or ) Tj 0.777778 0 Td 50.925926 Tz (methyl, ) Tj 52.857143 0 0 52.857143 0 2216.797203 Tm 7.586486 0 Td 51.238739 Tz (then ) Tj 1.456757 0 Td 70.945946 Tz (R. ) Tj 1.078378 0 Td 72.522523 Tz (R. ) Tj 1.059459 0 Td 56.756757 Tz (and ) Tj 1.248649 0 Td 72.522523 Tz (R ) Tj 0.87027 0 Td 48.348348 Tz (are ) Tj 1.002703 0 Td 52.552553 Tz (hydrogen. ) Tj 51.428571 0 0 51.428571 0 2175 Tm 7.097222 0 Td 42.12963 Tz (2. ) Tj 0.680556 0 Td 64.814815 Tz (The ) Tj 1.283333 0 Td 64.409722 Tz (compound ) Tj 3.208333 0 Td 59.953704 Tz (of ) Tj 0.797222 0 Td 53.148148 Tz (claim ) Tj 1.808333 0 Td 48.611111 Tz (1 ) Tj 0.505556 0 Td 54.62963 Tz (wherein ) Tj 2.527778 0 Td 74.537037 Tz (R ) Tj 0.875 0 Td 38.888889 Tz (is ) Tj 0.641667 0 Td 48.82716 Tz (trifluoromethyl ) Tj 51.428571 0 0 51.428571 0 2129.877698 Tm 6.358333 0 Td 58.333333 Tz (and ) Tj 1.263889 0 Td 74.537037 Tz (R. ) Tj 1.147222 0 Td 71.296296 Tz (R. ) Tj 1.069444 0 Td 58.333333 Tz (and ) Tj 1.283333 0 Td 74.537037 Tz (R ) Tj 0.875 0 Td 49.691358 Tz (are ) Tj 1.05 0 Td 54.012346 Tz (hydrogen. ) Tj 30 0 0 30 0 2547 Tm 41.666667 0 Td 75 Tz (10 ) Tj 30 0 0 30 0 2339 Tm 41.666667 0 Td 72.222222 Tz (15 ) Tj 52.857143 0 0 52.857143 0 2968 Tm 32.635135 0 Td 77.252252 Tz (28 ) Tj 51.428571 0 0 51.428571 0 2914.643693 Tm 26.016667 0 Td 43.75 Tz (3. ) Tj 0.680556 0 Td 64.814815 Tz (The ) Tj 1.283333 0 Td 64.00463 Tz (compound ) Tj 3.208333 0 Td 56.712963 Tz (of ) Tj 0.758333 0 Td 53.796296 Tz (claim ) Tj 1.769444 0 Td 48.611111 Tz (1 ) Tj 0.486111 0 Td 55.555556 Tz (wherein ) Tj 2.527778 0 Td 74.537037 Tz (R ) Tj 0.875 0 Td 58.333333 Tz (and ) Tj 1.225 0 Td 73.726852 Tz (Rare ) Tj 1.925 0 Td 47.685185 Tz (trifluo ) Tj 52.857143 0 0 52.857143 0 2877.677686 Tm 24.613514 0 Td 52.421171 Tz (romethyl ) Tj 2.705405 0 Td 57.807808 Tz (and ) Tj 1.22973 0 Td 72.522523 Tz (R ) Tj 0.87027 0 Td 57.807808 Tz (and ) Tj 1.248649 0 Td 69.369369 Tz (R ) Tj 0.832432 0 Td 48.348348 Tz (are ) Tj 1.040541 0 Td 52.552553 Tz (hydrogen. ) Tj 51.428571 0 0 51.428571 0 2835.687583 Tm 26.016667 0 Td 43.75 Tz (4. ) Tj 0.7 0 Td 63.734568 Tz (The ) Tj 1.283333 0 Td 64.00463 Tz (compound ) Tj 3.208333 0 Td 58.333333 Tz (of ) Tj 0.777778 0 Td 53.796296 Tz (claim ) Tj 1.827778 0 Td 48.611111 Tz (1 ) Tj 0.505556 0 Td 54.62963 Tz (wherein ) Tj 2.527778 0 Td 71.296296 Tz (R ) Tj 0.855556 0 Td 58.333333 Tz (and ) Tj 1.263889 0 Td 56.712963 Tz (Ra ) Tj 0.894444 0 Td 49.691358 Tz (are ) Tj 1.011111 0 Td 51.851852 Tz (chloro ) Tj 52.857143 0 0 52.857143 0 2797.418803 Tm 24.613514 0 Td 56.756757 Tz (and ) Tj 1.210811 0 Td 72.522523 Tz (R ) Tj 0.87027 0 Td 57.807808 Tz (and ) Tj 1.22973 0 Td 72.522523 Tz (R ) Tj 0.87027 0 Td 48.348348 Tz (are ) Tj 1.002703 0 Td 52.552553 Tz (hydrogen. ) Tj 51.428571 0 0 51.428571 0 2757.920635 Tm 26.016667 0 Td 43.75 Tz (5. ) Tj 0.680556 0 Td 62.654321 Tz (The ) Tj 1.263889 0 Td 64.00463 Tz (compound ) Tj 3.208333 0 Td 55.092593 Tz (of ) Tj 0.738889 0 Td 53.148148 Tz (claim ) Tj 1.808333 0 Td 45.37037 Tz (1 ) Tj 0.447222 0 Td 55.555556 Tz (wherein ) Tj 2.547222 0 Td 74.537037 Tz (R ) Tj 0.875 0 Td 37.268519 Tz (is ) Tj 0.583333 0 Td 54.62963 Tz (halogen ) Tj 2.45 0 Td 58.333333 Tz (and ) Tj 1.244444 0 Td 72.916667 Tz (R. ) Tj 52.857143 0 0 52.857143 0 2718.75 Tm 24.632432 0 Td 74.099099 Tz (R, ) Tj 1.078378 0 Td 56.756757 Tz (and ) Tj 1.248649 0 Td 69.369369 Tz (R ) Tj 0.832432 0 Td 49.399399 Tz (are ) Tj 1.040541 0 Td 52.552553 Tz (hydrogen. ) Tj 51.428571 0 0 51.428571 0 2678.042003 Tm 26.036111 0 Td 42.12963 Tz (6. ) Tj 0.7 0 Td 63.734568 Tz (The ) Tj 1.302778 0 Td 64.00463 Tz (compound ) Tj 3.247222 0 Td 56.712963 Tz (of ) Tj 0.797222 0 Td 53.148148 Tz (claim ) Tj 1.788889 0 Td 58.333333 Tz (5 ) Tj 0.544444 0 Td 55.555556 Tz (wherein ) Tj 2.566667 0 Td 74.537037 Tz (R ) Tj 0.894444 0 Td 38.888889 Tz (is ) Tj 0.680556 0 Td 47.962963 Tz (iodo. ) Tj 52.857143 0 0 52.857143 0 2637.92343 Tm 25.313514 0 Td 42.567568 Tz (7. ) Tj 0.7 0 Td 60.960961 Tz (The ) Tj 1.267568 0 Td 61.880631 Tz (compound ) Tj 3.159459 0 Td 56.756757 Tz (of ) Tj 0.756757 0 Td 51.711712 Tz (claim ) Tj 1.759459 0 Td 56.756757 Tz (5 ) Tj 0.510811 0 Td 54.504505 Tz (wherein ) Tj 2.478378 0 Td 78.828829 Tz (R ) Tj 0.908108 0 Td 39.414414 Tz (is ) Tj 0.643243 0 Td 46.846847 Tz (chloro. ) Tj 51.428571 0 0 51.428571 0 2598.685906 Tm 26.016667 0 Td 43.75 Tz (8. ) Tj 0.661111 0 Td 63.734568 Tz (The ) Tj 1.263889 0 Td 63.599537 Tz (compound ) Tj 3.208333 0 Td 53.472222 Tz (of ) Tj 0.738889 0 Td 53.148148 Tz (claim ) Tj 1.769444 0 Td 48.611111 Tz (1 ) Tj 0.486111 0 Td 54.62963 Tz (wherein ) Tj 2.508333 0 Td 74.537037 Tz (R ) Tj 0.836111 0 Td 58.333333 Tz (and ) Tj 1.225 0 Td 71.296296 Tz (R ) Tj 0.855556 0 Td 59.259259 Tz (combine ) Tj 2.644444 0 Td 43.75 Tz (to ) Tj 52.857143 0 0 52.857143 0 2558.923077 Tm 24.613514 0 Td 55.968468 Tz (form ) Tj 1.551351 0 Td 46.812197 Tz (dithiadiazole ) Tj 3.783784 0 Td 59.90991 Tz (and ) Tj 1.248649 0 Td 69.369369 Tz (R ) Tj 0.889189 0 Td 56.756757 Tz (and ) Tj 1.22973 0 Td 48.873874 Tz (Ra ) Tj 0.87027 0 Td 48.348348 Tz (are ) Tj 1.002703 0 Td 52.552553 Tz (hydrogen. ) Tj 51.428571 0 0 51.428571 0 2520.708333 Tm 26.016667 0 Td 43.75 Tz (9. ) Tj 0.680556 0 Td 64.814815 Tz (The ) Tj 1.283333 0 Td 64.00463 Tz (compound ) Tj 3.208333 0 Td 56.712963 Tz (of ) Tj 0.758333 0 Td 53.796296 Tz (claim ) Tj 1.769444 0 Td 48.611111 Tz (1 ) Tj 0.486111 0 Td 55.555556 Tz (wherein ) Tj 2.527778 0 Td 74.537037 Tz (R ) Tj 0.875 0 Td 58.333333 Tz (and ) Tj 1.225 0 Td 73.726852 Tz (Rare ) Tj 1.944444 0 Td 55.092593 Tz (methyl ) Tj 52.857143 0 0 52.857143 0 2479.418803 Tm 24.613514 0 Td 56.756757 Tz (and ) Tj 1.210811 0 Td 72.522523 Tz (R ) Tj 0.87027 0 Td 57.807808 Tz (and ) Tj 1.22973 0 Td 72.522523 Tz (R ) Tj 0.87027 0 Td 48.348348 Tz (are ) Tj 1.002703 0 Td 52.552553 Tz (hydrogen. ) Tj 51.428571 0 0 51.428571 0 2437.998647 Tm 26.055556 0 Td 48.611111 Tz (10. ) Tj 1.05 0 Td 64.814815 Tz (The ) Tj 1.361111 0 Td 64.409722 Tz (compound ) Tj 3.286111 0 Td 59.953704 Tz (of ) Tj 0.816667 0 Td 53.148148 Tz (claim ) Tj 1.847222 0 Td 51.851852 Tz (1 ) Tj 0.563889 0 Td 55.092593 Tz (wherein ) Tj 2.586111 0 Td 74.537037 Tz (R ) Tj 0.933333 0 Td 38.888889 Tz (is ) Tj 0.7 0 Td 54.62963 Tz (halogen ) Tj 2.488889 0 Td 60.493827 Tz (and ) Tj 52.857143 0 0 52.857143 0 2396.191489 Tm 24.632432 0 Td 72.522523 Tz (R. ) Tj 1.135135 0 Td 69.369369 Tz (R. ) Tj 1.040541 0 Td 56.756757 Tz (and ) Tj 1.22973 0 Td 53.603604 Tz (Ra ) Tj 0.851351 0 Td 50.45045 Tz (are ) Tj 1.040541 0 Td 52.552553 Tz (hydrogen. ) Tj 51.428571 0 0 51.428571 0 2354.009479 Tm 26.055556 0 Td 48.611111 Tz (11. ) Tj 1.030556 0 Td 63.734568 Tz (The ) Tj 1.302778 0 Td 64.409722 Tz (compound ) Tj 3.266667 0 Td 58.333333 Tz (of ) Tj 0.777778 0 Td 53.148148 Tz (claim ) Tj 1.847222 0 Td 48.611111 Tz (1 ) Tj 0.505556 0 Td 55.092593 Tz (wherein ) Tj 2.566667 0 Td 71.296296 Tz (R ) Tj 0.913889 0 Td 37.268519 Tz (is ) Tj 0.661111 0 Td 47.314815 Tz (iodo. ) Tj 51.428571 0 0 51.428571 0 2311.725916 Tm 26.055556 0 Td 48.611111 Tz (12. ) Tj 1.030556 0 Td 64.814815 Tz (The ) Tj 1.341667 0 Td 64.409722 Tz (compound ) Tj 3.247222 0 Td 59.953704 Tz (of ) Tj 0.797222 0 Td 53.796296 Tz (claim ) Tj 1.866667 0 Td 48.611111 Tz (1 ) Tj 0.525 0 Td 55.092593 Tz (wherein ) Tj 2.586111 0 Td 74.537037 Tz (R ) Tj 0.875 0 Td 60.493827 Tz (and ) Tj 1.302778 0 Td 56.712963 Tz (Ra ) Tj 0.894444 0 Td 50.771605 Tz (are ) Tj 1.108333 0 Td 46.990741 Tz (trif ) Tj 52.857143 0 0 52.857143 0 2272.973783 Tm 24.613514 0 Td 52.170352 Tz (luoromethyl ) Tj 3.613514 0 Td 57.807808 Tz (and ) Tj 1.22973 0 Td 72.522523 Tz (R ) Tj 0.87027 0 Td 57.807808 Tz (and ) Tj 1.248649 0 Td 69.369369 Tz (R ) Tj 0.832432 0 Td 49.399399 Tz (are ) Tj 1.040541 0 Td 52.552553 Tz (hydrogen. ) Tj 51.428571 0 0 51.428571 0 2230.913376 Tm 26.055556 0 Td 48.611111 Tz (13. ) Tj 0.972222 0 Td 64.814815 Tz (The ) Tj 1.263889 0 Td 64.00463 Tz (compound ) Tj 3.208333 0 Td 51.851852 Tz (of ) Tj 0.7 0 Td 53.148148 Tz (claim ) Tj 1.769444 0 Td 48.611111 Tz (1 ) Tj 0.447222 0 Td 56.018519 Tz (wherein ) Tj 2.488889 0 Td 74.537037 Tz (R ) Tj 0.875 0 Td 37.268519 Tz (is ) Tj 0.583333 0 Td 48.82716 Tz (trifluoromethyl ) Tj 52.857143 0 0 52.857143 0 2187.727689 Tm 24.613514 0 Td 56.756757 Tz (and ) Tj 1.248649 0 Td 70.945946 Tz (R. ) Tj 1.097297 0 Td 69.369369 Tz (R. ) Tj 1.021622 0 Td 56.756757 Tz (and ) Tj 1.267568 0 Td 71.734234 Tz (Rare ) Tj 1.891892 0 Td 52.202202 Tz (hydrogen. ) Tj 24.285714 0 0 24.285714 0 2139 Tm 67.323529 0 Td 68.627451 Tz (k ) Tj 2.305882 0 Td 68.627451 Tz (k ) Tj 2.347059 0 Td 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