Synthesis, biological evaluation, and metabolic stability of acrylamide derivatives as novel CCR3 antagonists

Our laboratory has identified several acrylamide derivatives with potent CCR3 inhibitory activity. In the present study, we evaluated the in vitro metabolic stability (CLint; mL/min/kg) of these compounds in human liver microsomes (HLMs), and assessed the relationship between their structures and CLint values. Among the compounds identified, N-{(3R)-1-[(6-fluoro-2-naphthyl)methyl]pyrrolidin-3-yl}-2-[1-(2-hydroxybenzoyl)piperidin-4-ylidene]acetamide (30j) was found to be a potent inhibitor (IC50 = 8.4 nM) with a high metabolic stability against HLMs.

Acrylamide derivatives were prepared, and their inhibitory activity against CCR3 and in vitro metabolic stability against human liver microsomes (HLMs) were evaluated.Figure optionsDownload as PowerPoint slide