Discovery of potent and selective succinyl hydroxamate inhibitors of matrix metalloprotease-3 (stromelysin-1)

被引：24
|
作者：
Fray, MJ [1 ]
Dickinson, RP [1 ]
机构：
[1] Pfizer Global Res & Dev, Dept Discovery Chem, Sandwich CT13 9NJ, Kent, England
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2001年 / 11卷 / 04期
关键词：
D O I：
10.1016/S0960-894X(00)00720-4
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Structure-activity relationships are described for a series of succinyl hydroxamic acids 4a-o as potent and selective inhibitors of matrix metalloprotease-3 (stromelysin-1). Optimisation of P1' and P3' groups gave compound 4j (MMP-3 IC50 = 5.9nM) which was >140-fold less potent against MMP-1 (IC50 = 51,000nM), MMP-2 (IC50=1790nM), MMP-9 (IC50 = 840 nM) and MMP-14 (IC50 = 1900 nM). (C) 2001 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码：571 / 574
页数：4
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