Discovery of 3,5-bis(trifluoromethyl)benzyl L-arylglycinamide based potent CCR2 antagonists

被引：28

作者：

Yang, LH ^{[1
]}

Zhou, CY ^{[1
]}

Guo, LQ ^{[1
]}

Morriello, G ^{[1
]}

Butora, G ^{[1
]}

Pasternak, A ^{[1
]}

Parsons, WH ^{[1
]}

Mills, SG ^{[1
]}

MacCoss, M ^{[1
]}

Vicario, PP ^{[1
]}

Zweerink, H ^{[1
]}

Ayala, JM ^{[1
]}

Goyal, S ^{[1
]}

Hanlon, WA ^{[1
]}

Cascieri, MA ^{[1
]}

Springer, MS ^{[1
]}

机构：

[1] Merck Res Labs, Rahway, NJ 07065 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2006年 / 16卷 / 14期

关键词：

CCR2; CCR2b; MCP-1; CCL2; antagonist; chemokine; chemotaxis; GPCR;

D O I：

10.1016/j.bmcl.2006.04.045

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Systematic modification of a screening lead yielded a class of potent glycinamide based CCR2 antagonists. The best compound (55, (2S)-N-[3,5-bis(trifluoromethyl)benzyl]-2-{[2-(1-piperidinyl)ethyl]amino}-2-(3-thienyl)acetamide) displayed good binding affinity (IC50 = 30 and 39 nM) toward human monocytes and CHO cell expressing human CCR2b, respectively. Functionally, it blocked MCP-1 (CCL2)-induced calcium mobilization (IC50 = 50 nM) and chemotaxis mediated through the CCR2 receptor (9.6 nM). It is selective against other chemokine receptors tested. (c) 2006 Elsevier Ltd. All rights reserved.

引用

收藏

页码：3735 / 3739

页数：5

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