4区 · 医学
Article
作者: Guo, Liangqin ; Hanlon, William A. ; Pasternak, Alexander ; Mills, Sander G. ; Goyal, Shefali ; Vicario, Pasquale P. ; Zweerink, Hans ; MacCoss, Malcolm ; Zhou, Changyou ; Cascieri, Margaret A. ; Yang, Lihu ; Butora, Gabor ; Morriello, Gregori ; Ayala, Julia M. ; Parsons, William H. ; Springer, Marty S.
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.