| Autor: |
Dillard, R. D., Bach, N. J., Draheim, S. E., Berry, D. R., Carlson, D. G., Chirgadze, N. Y., Clawson, D. K., Hartley, L. W., Johnson, L. M., Jones, N. D., McKinney, E. R., Mihelich, E. D., Olkowski, J. L., Schevitz, R. W., Smith, A. C., Snyder, D. W., Sommers, C. D., Wery, J.-P. |
| Zdroj: |
Journal of Medicinal Chemistry; December 20, 1996, Vol. 39 Issue: 26 p5119-5136, 18p |
| Abstrakt: |
Phospholipases (PLAs) produce rate-limiting precursors in the biosynthesis of various types of biologically active lipids involved in inflammatory processes. Increased levels of human nonpancreatic secretory phospholipase A2 (hnps-PLA2) have been detected in several pathological conditions. An inhibitor of this enzyme could have therapeutic utility. A broad screening program was carried out to identify chemical structures which could inhibit hnps-PLA2. One of the lead compounds generated by the screening program was 5-methoxy-2-methyl-1-(phenylmethyl)-1H-indole-3-acetic acid (13a). We describe the syntheses, structure−activity relationships, and pharmacological activities of a series of indole-3-acetamides and related compounds derived from this lead. This SAR was undertaken with the aid of X-ray crystal structures of complexes between the inhibitors and hnps-PLA2 which were of great value in directing the SAR. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
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