Conversion of potent MMP inhibitors into selective TACE inhibitors

被引：24

作者：

Cherney, RJ ^{[1
]}

King, BW ^{[1
]}

Gilmore, JL ^{[1
]}

Liu, RQ ^{[1
]}

Covington, MB ^{[1
]}

Duan, JJW ^{[1
]}

Decicco, CP ^{[1
]}

机构：

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

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2006年 / 16卷 / 04期

关键词：

TACE inhibitor; ADAM-17; inhibitor;

D O I：

10.1016/j.bmcl.2005.10.078

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Novel sultam hydroxamates with potent MMP activity were transformed into potent TACE inhibitors, lacking MMP activity. To accomplish this we relied on structural differences between the MMP and TACE Sl' pockets and the known advantageous tit of a 2-methyl-4-quinolinylmethoxyphenyl group into this region. From this approach, compound 7d was identified as a potent TACE inhibitor (IC50 = 3.7 nM) that lacked MMP-1, -2, -9, and -13 activity. (c) 2005 Elsevier Ltd. All rights reserved.

引用

页码：1028 / 1031

页数：4

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