Potent and selective carboxylic acid-based inhibitors of matrix metalloproteinases

被引：54

作者：

Pikul, S ^{[1
]}

Ohler, NE ^{[1
]}

Ciszewski, G ^{[1
]}

Laufersweiler, MC ^{[1
]}

Almstead, NG ^{[1
]}

De, B ^{[1
]}

Natchus, MG ^{[1
]}

Hsieh, LC ^{[1
]}

Janusz, MJ ^{[1
]}

Peng, SX ^{[1
]}

Branch, TM ^{[1
]}

King, SL ^{[1
]}

Taiwo, YO ^{[1
]}

Mieling, GE ^{[1
]}

机构：

[1] Procter & Gamble Pharmaceut, Hlth Care Res Ctr, Mason, OH 45040 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2001年 / 44卷 / 16期

关键词：

D O I：

10.1021/jm015531s

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A novel series of carboxylic acids containing a substituted piperidine were synthesized and tested for inhibition of selected matrix metalloproteinases. Multiple analogues prepared based on this novel design were found to inhibit the target MMPs (MMP-2, -3, -8, -9, and -13) with unprecedented, low nanomolar potency while, at the same time, sparing MMP-1 and MMP-7. Solubility and plasma protein binding of several members of this new series of carboxylic acids were also investigated.

引用

页码：2499 / 2502

页数：4

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