Discovery of trisubstituted cyclohexanes as potent CC chemokine receptor 2 (CCR2) antagonists

被引：21

作者：

Cherney, Robert J. ^{[1
]}

Brogan, John B. ^{[2
]}

Mo, Ruowei ^{[1
]}

Lo, Yvonne C. ^{[1
]}

Yang, Gengjie ^{[1
]}

Miller, Persymphonie B. ^{[1
]}

Scherle, Peggy A. ^{[1
]}

Molino, Bruce F. ^{[2
]}

Carter, Percy H. ^{[1
]}

Decicco, Carl P. ^{[1
]}

机构：

[1] Bristol Myers Squibb Co, Res & Dev, Princeton, NJ 08543 USA

[2] AMRI, Albany, NY 12212 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2009年 / 19卷 / 03期

关键词：

CCR2; antagonist; Chemokines; MCP-1; MONOCYTE CHEMOATTRACTANT PROTEIN-1; DISEASE;

D O I：

10.1016/j.bmcl.2008.12.062

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of trisubstituted cyclohexanes was designed, synthesized and evaluated as CC chemokine receptor 2 (CCR2) antagonists. This led to the identification of two distinct substitution patterns about the cyclohexane ring as potent and selective CCR2 antagonists. Compound 36 exhibited excellent binding ( CCR2 IC50 = 2.4 nM) and functional antagonism ( calcium flux IC50 = 2.0 nM and chemotaxis IC50 = 5.1 nM). (c) 2008 Elsevier Ltd. All rights reserved.

引用

页码：597 / 601

页数：5

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