Phosphinic acid-based MMP-13 inhibitors that spare MMP-1 and MMP-3

被引：33
|
作者：
Reiter, LA [1 ]
Mitchell, PG [1 ]
Martinelli, GJ [1 ]
Lopresti-Morrow, LL [1 ]
Yocum, SA [1 ]
Eskra, JD [1 ]
机构：
[1] Pfizer Inc, Global Res & Dev, Groton Labs, Groton, CT 06340 USA
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2003年 / 13卷 / 14期
关键词：
D O I：
10.1016/S0960-894X(03)00413-X
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Phosphinic acid-based inhibitors of MMP-13 have been investigated with the aim of identifying potent inhibitors with high selectivity versus MMP-1. Independent variation of the substituents on a P-1' phenethyl group and a P-2 benzyl group improved potencies in both cases around 3-fold over the unsubstituted parent. Combining improved P-1' and P-2 groups into a single molecule gave an inhibitor with a 4.5 nM IC50 against MMP-13 and which is 270-fold selective over MMP-1. (C) 2003 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码：2331 / 2336
页数：6
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