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
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
收藏
页码:2499 / 2502
页数:4
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