Non-hydroxamate 5-phenylpyrimidine-2,4,6-trione derivatives as selective inhibitors of tumor necrosis factor-α converting enzyme

被引：33

作者：

Duan, JJW ^{[1
]}

Lu, ZH ^{[1
]}

Wasserman, ZR ^{[1
]}

Liu, RQ ^{[1
]}

Covington, MB ^{[1
]}

Decicco, CP ^{[1
]}

机构：

[1] Bristol Myers Squibb Pharmaceut Res Inst, Princeton, NJ 08543 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2005年 / 15卷 / 12期

关键词：

D O I：

10.1016/j.bmcl.2005.04.039

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

New inhibitors of tumor necrosis factor-a converting enzyme (TACE) were discovered with a pyrimidine-2,4,6-trione in place of the commonly used hydroxamic acid. These non-hydroxamate TACE inhibitors were developed by incorporating a 4-(2methyl-4-quinolinylmethoxy)phenyl group, an optimized TACE selective P1' group. Several leads were identified with IC50 values around 100 nM in a porcine TACE assay and selective over MMP-1, -2, -9, -13, and aggrecanase. (c) 2005 Elsevier Ltd. All rights reserved.

引用

页码：2970 / 2973

页数：4

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