Document Report Card

ID: ALA1129458

Journal: J Med Chem

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

Authors: Draheim SE, Bach NJ, Dillard RD, Berry DR, Carlson DG, Chirgadze NY, Clawson DK, Hartley LW, Johnson LM, Jones ND, McKinney ER, Mihelich ED, Olkowski JL, Schevitz RW, Smith AC, Snyder DW, Sommers CD, Wery JP.

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.

CiteXplore: 8978844

DOI: 10.1021/jm960487f