α-Aminothiazole-γ-aminobutanoic amides as potent, small molecule CCR2 receptor antagonists

详细信息    查看全文

• 作者：Changyou Zhou ; Liangqin Guo ; William H. Parsons ; S ; er G. Mills ; Malcolm MacCoss ; Pasquale P. Vicario ; Hans Zweerink ; Margaret A. Cascieri ; Martin S. Springer ; Lihu Yang
• 关键词：CCR2 ; Antagonist ; Aminothiazole ; Chemotaxis ; Monocyte
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2007
• 出版时间：15 January 2007
• 年：2007
• 卷：17
• 期：2
• 页码：309-314
• 全文大小：163 K

文摘

A series of racemic and homochiral α-aminothiazole-γ-aminobutyroamides that display high affinities for human and murine CCR2 and functional antagonism by inhibition of monocyte recruitment are described. A representative example is (2S)-2-[2-(acetylamino)-1,3-thiazol-4-yl]-N-[3-methyl-5-(trifluoromethyl)benzyl]-4-(4-phenylpiperidin-1-yl)butanamide, which shows 5 nM affinity for human monocytes and CHO cells expressing the human CCR2b receptor. It also inhibited MCP-1 initiated chemotaxis of human monocytes with an IC₅₀ of 0.69 nM.