Potent heteroarylpiperidine and carboxyphenylpiperidine 1-alkyl-cyclopentane carboxamide CCR2 antagonists

This report describes replacement of the 4-(4-fluorophenyl)piperidine moiety in our CCR2 antagonists with 4-heteroaryl piperidine and 4-(carboxyphenyl)-piperidine subunits. Some of the resulting analogs retained potency in our CCR2 binding assay and had improved selectivity versus the IKr channel; poor selectivity against IKr had been a liability of earlier analogs in this series.

Graphical abstractThis report describes incorporation of 4-heteroaryl piperidine and 4-(carboxyphenyl)-piperidine subunits into our CCR2 antagonists, leading to new analogs retaining CCR2 potency, but with improved selectivity over IKr channel binding.Figure optionsDownload full-size imageDownload as PowerPoint slide