Indole inhibitors of human nonpancreatic secretory phospholipase A2. 3. Indole-3-glyoxamides

  • J Med Chem. 1996 Dec 20;39(26):5159-75. doi: 10.1021/jm960487f.
S E Draheim  1 ,  N J Bach ,  R D Dillard ,  D R Berry ,  D G Carlson ,  N Y Chirgadze ,  D K Clawson ,  L W Hartley ,  L M Johnson ,  N D Jones ,  E R McKinney ,  E D Mihelich ,  J L Olkowski ,  R W Schevitz ,  A C Smith ,  D W Snyder ,  C D Sommers ,  J P Wery
Affiliations
  • 1. Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana 46285, USA.
PMID: 8978844 DOI: 10.1021/jm960487f
Abstract

The preceding papers of this series detail the development of functionalized indole-3-acetamides as inhibitors of hnps-PLA2. We describe here the extension of the structure-activity relationship to include a series of indole-3-glyoxamide derivatives. Functionalized indole-3-glyoxamides with an acidic substituent appended to the 4- or 5-position of the indole ring were prepared and tested as inhibitors of hnps-PLA2. It was found that the indole-3-glyoxamides with a 4-oxyacetic acid substituent had optimal inhibitory activity. These inhibitors exhibited an improvement in potency over the best of the indole-3-acetamides, and LY315920 (6m) was selected for evaluation clinically as an hnps-PLA2 inhibitor.

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