Indole inhibitors of human nonpancreatic secretory phospholipase A(2) .3. Indole-3-glyoxamides
Indole inhibitors of human nonpancreatic secretory phospholipase A(2) .3. Indole-3-glyoxamides
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DOI：
10.1021/jm960487f
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发表时间：
1996-12-20
影响因子：
7.3
通讯作者：
Wery, JP
中科院分区：
文献类型：
--
作者：
Draheim, SE;Bach, NJ;Wery, JP
本系列的前几篇论文详细介绍了功能化吲哚-3-乙酰酰胺作为hnps-PLA抑制剂的研究进展(2)。我们在这里描述了结构-活性关系的扩展，包括一系列吲哚-3-乙氧酰胺衍生物。在吲哚环的4位或5位上附加一个酸性取代基的功能化吲哚-3-乙酰酰胺被制备并测试为hnps-PLA的抑制剂(2)。结果表明，含4-氧乙酸取代基的吲哚-3-乙氧酰胺具有最佳的抑菌活性。这些抑制剂的效价优于吲哚-3-乙酰酰胺，因此LY315920 （6m）被选择作为hnps-PLA(2)抑制剂进行临床评估。
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.