Sultam hydroxamates as novel matrix metalloproteinase inhibitors

被引：93

作者：

Cherney, RJ ^{[1
]}

Mo, RW ^{[1
]}

Meyer, DT ^{[1
]}

Hardman, KD ^{[1
]}

Liu, RQ ^{[1
]}

Covington, MB ^{[1
]}

Qian, MX ^{[1
]}

Wasserman, ZR ^{[1
]}

Christ, DD ^{[1
]}

Trzaskos, JM ^{[1
]}

Newton, RC ^{[1
]}

Decicco, CP ^{[1
]}

机构：

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

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2004年 / 47卷 / 12期

关键词：

D O I：

10.1021/jm049833g

中图分类号：

R914 [药物化学];

学科分类号：

100701 [药物化学];

摘要：

In this communication we describe the design, synthesis, and evaluation of novel sultam hydroxamates 4 as MMP-2, -9, and -13 inhibitors. Compound 26 was found to be an active inhibitor (NIMP-2 IC50 = 1 nM) with 1000-fold selectivity over MMP-1 and good oral bioavailability (F = 43%) in mouse. An X-ray crystal structure of 26 in MMP-13 confirms the key hydrogen bonds and prime side binding in the active site.

引用

页码：2981 / 2983

页数：3

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