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

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• 作者：Robert J. Cherney ; John B. Brogan ; Ruowei Mo ; Yvonne C. Lo ; Gengjie Yang ; Persymphonie B. Miller ; Peggy A. Scherle ; Bruce F. Molino ; Percy H. Carter ; Carl P. Decicco
• 关键词：CCR2 antagonist ; Chemokines ; MCP-1
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2009
• 出版时间：1 February 2009
• 年：2009
• 卷：19
• 期：3
• 页码：597-601
• 全文大小：567 K

文摘

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).