Heteroalicyclic carboxamidines as inhibitors of inducible nitric oxide synthase; the identification of (2R)-2-pyrrolidinecarboxamidine as a potent and selective haem-co-ordinating inhibitor

被引：2

作者：

Young, Robert J. ^{[1
]}

Alderton, Wendy ^{[1
]}

Angell, Anthony D. R. ^{[1
]}

Beswick, Paul J. ^{[1
]}

Brown, David ^{[1
]}

Chambers, C. Lynn ^{[1
]}

Crowe, Miriam C. ^{[1
]}

Dawson, John ^{[1
]}

Hamlett, Christopher C. F. ^{[1
]}

Hodgson, Simon T. ^{[1
]}

Kleanthous, Savvas ^{[1
]}

Knowles, Richard G. ^{[1
]}

Russell, Linda J. ^{[1
]}

Stocker, Richard ^{[1
]}

Woolven, James M. ^{[1
]}

机构：

[1] GlaxoSmithKline R&D, Med Res Ctr, Stevenage SG1 2NY, Herts, England

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2011年 / 21卷 / 10期

关键词：

Nitric oxide synthase; Iron co-ordinating inhibitors; CRYSTAL-STRUCTURE; ISOFORMS; INACTIVATION; SUBSTRATE; MECHANISM; DISEASES; REVEALS; PTERIN;

D O I：

10.1016/j.bmcl.2011.03.038

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Heteroalicyclic carboxamidines were synthesised and evaluated as inhibitors of nitric oxide synthases. (2R)-2-Pyrrolidinecarboxamidine, in particular, was shown to be a highly potent in vitro (IC(50) = 0.12 mu M) and selective iNOS inhibitor (> 100-fold vs both eNOS and nNOS), with probable binding to the key anchoring glutamate residue and co-ordination to the haem iron. (C) 2011 Elsevier Ltd. All rights reserved.

引用

页码：3037 / 3040

页数：4

共 6 条

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