BMS-813160: A Potent CCR2 and CCR5 Dual Antagonist Selected as a Clinical Candidate
Robert J. Cherney, Prakash Anjanappa, K. Selvakumar, Douglas G. Batt, Gregory D. Brown, Anne Rose, Ragini Vuppugalla, Jing Chen, Jian Pang, Songmei Xu, Melissa Yarde, Andrew J. Tebben, Venkatram Reddy Paidi, Mary Ellen Cvijic, Arvind Mathur, Joel C. Barrish, Sandhya Mandlekar, Qihong Zhao, Percy H. Carter
Abstract
BMS-813160 (compound 3) was identified as a potent and selective CCR2/5 dual antagonist. Compound 3 displayed good permeability at pH = 7.4 in PAMPA experiments and demonstrated excellent human liver microsome stability. Pharmacokinetic studies established that 3 had excellent oral bioavailability and exhibited low clearance in dog and cyno. Compound 3 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 3 was selected as a clinical candidate.