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.
Robert J Cherney  1 ,  Prakash Anjanappa  2 ,  Kumaravel Selvakumar  2 ,  Douglas G Batt  1 ,  Gregory D Brown  1 ,  Anne V Rose  1 ,  Ragini Vuppugalla  1 ,  Jing Chen  1 ,  Jian Pang  1 ,  Songmei Xu  1 ,  Melissa Yarde  1 ,  Andrew J Tebben  1 ,  Venkatram Reddy Paidi  2 ,  Mary Ellen Cvijic  1 ,  Arvind Mathur  1 ,  Joel C Barrish  1 ,  Sandhya Mandlekar  1 ,  Qihong Zhao  1 ,  Percy H Carter  1
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.
PMID: 34795864 DOI: 10.1021/acsmedchemlett.1c00373
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.

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