Capped diaminopropionamide-glycine dipeptides are inhibitors of CC chemokine receptor 2 (CCR2)

被引：16

作者：

Carter, Percy H. ^{[1
]}

Brown, Gregory D. ^{[1
]}

Friedrich, Sarah R. ^{[1
]}

Cherney, Robert J. ^{[1
]}

Tebben, Andrew J. ^{[1
]}

Lo, Yvonne C. ^{[1
]}

Yang, Gengjie ^{[1
]}

Jezak, Heather ^{[1
]}

Solomon, Kimberly A. ^{[1
]}

Scherle, Peggy A. ^{[1
]}

Decicco, Carl P. ^{[1
]}

机构：

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

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2007年 / 17卷 / 19期

关键词：

CCR2; small molecule; antagonist; G-protein coupled receptor; chemokine; inflammation;

D O I：

10.1016/j.bmcl.2007.07.028

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A new series of CCR2 antagonists has been discovered that incorporates intramolecular hydrogen bonding as a strategy for rigidifying the scaffold. The structure-activity relationship was established through initial systematic modification of substitution pattern and chain length, followed by independent optimization of three different substituents (benzylamine, carboxamide, and benzamide). Several of the acyclic compounds display 10-30 nM binding affinity for CCR2. Moreover, these antagonists are able to block both MCP-1-induced Ca2+ flux and monocyte chemotaxis, and are selective for binding to CCR2 over CCR1 and CCR3. (C) 2007 Elsevier Ltd. All rights reserved.

引用

页码：5455 / 5461

页数：7

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