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

Robert J Cherney; Prakash Anjanappa; Kumaravel Selvakumar; Douglas G Batt; Gregory D Brown; Anne V 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

doi:10.1021/acsmedchemlett.1c00373

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

ACS Med Chem Lett. 2021 Oct 15;12(11):1753-1758. doi: 10.1021/acsmedchemlett.1c00373. eCollection 2021 Nov 11.

Authors

Robert J Cherney¹, Prakash Anjanappa², Kumaravel Selvakumar², Douglas G Batt¹, Gregory D Brown¹, Anne V Rose¹, Ragini Vuppugalla¹, Jing Chen¹, Jian Pang¹, Songmei Xu¹, Melissa Yarde¹, Andrew J Tebben¹, Venkatram Reddy Paidi², Mary Ellen Cvijic¹, Arvind Mathur¹, Joel C Barrish¹, Sandhya Mandlekar¹, Qihong Zhao¹, Percy H Carter¹

Affiliations

¹ Bristol Myers Squibb Company, Research and Early Development, Princeton, New Jersey 08540-4000, United States.
² Biocon Bristol Myers Squibb Research and Development Center, Bangalore 560099, India.

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.