Indole inhibitors of human nonpancreatic secretory phospholipase A(2) .3. Indole-3-glyoxamides

被引：70

作者：

Draheim, SE ^{[1
]}

Bach, NJ ^{[1
]}

Dillard, RD ^{[1
]}

Berry, DR ^{[1
]}

Carlson, DG ^{[1
]}

Chirgadze, NY ^{[1
]}

Clawson, DK ^{[1
]}

Hartley, LW ^{[1
]}

Johnson, LM ^{[1
]}

Jones, ND ^{[1
]}

McKinney, ER ^{[1
]}

Mihelich, ED ^{[1
]}

Olkowski, JL ^{[1
]}

Schevitz, RW ^{[1
]}

Smith, AC ^{[1
]}

Snyder, DW ^{[1
]}

Sommers, CD ^{[1
]}

Wery, JP ^{[1
]}

机构：

[1] ELI LILLY & CO,LILLY CORP CTR,LILLY RES LABS,INDIANAPOLIS,IN 46285

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1996年 / 39卷 / 26期

关键词：

D O I：

10.1021/jm960487f

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The preceding papers of this series detail the development of functionalized indole-3-acetamides as inhibitors of hnps-PLA(2). 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-PLA(2). 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-PLA(2) inhibitor.

引用

页码：5159 / 5175

页数：17

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