BMS-813160: A Potent CCR2 and CCR5 Dual Antagonist Selected as a Clinical Candidate

Abstract

BMS-813160 (compound <b>3</b>) was identified as a potent and selective CCR2/5 dual antagonist. Compound <b>3</b> displayed good permeability at pH = 7.4 in PAMPA experiments and demonstrated excellent human liver microsome stability. Pharmacokinetic studies established that <b>3</b> had excellent oral bioavailability and exhibited low clearance in dog and cyno. Compound <b>3</b> was also studied in the mouse thioglycollate-induced peritonitis model, which confirmed its ability to inhibit the migration of inflammatory monocytes and macrophages. As a result of this profile, compound <b>3</b> was selected as a clinical candidate.