Discovery of INCB10820/PF-4178903, a potent, selective, and orally bioavailable dual CCR2 and CCR5 antagonist

  • Bioorg Med Chem Lett. 2011 Mar 1;21(5):1442-6. doi: 10.1016/j.bmcl.2011.01.015.
Changsheng Zheng  1 ,  Ganfeng Cao ,  Michael Xia ,  Hao Feng ,  Joseph Glenn ,  Rajan Anand ,  Ke Zhang ,  Taisheng Huang ,  Anlai Wang ,  Ling Kong ,  Mei Li ,  Laurine Galya ,  Robert O Hughes ,  Rajesh Devraj ,  Phillip A Morton ,  D Joseph Rogier ,  Maryanne Covington ,  Fred Baribaud ,  Niu Shin ,  Peggy Scherle ,  Sharon Diamond ,  Swamy Yeleswaram ,  Kris Vaddi ,  Robert Newton ,  Greg Hollis ,  Steven Friedman ,  Brian Metcalf ,  Chu-Biao Xue
Affiliations
  • 1. Incyte Corporation, Experimental Station E336, Wilmington, DE 19880, USA.
PMID: 21295478 DOI: 10.1016/j.bmcl.2011.01.015
Abstract

We report the discovery of a potent, selective, and orally bioavailable dual CCR2 and CCR5 Antagonist (3S,4S)-N-[(1R,3S)-3-isopropyl-3-({4-[4-(trifluoromethyl)pyridin-2-yl]piperazin-1-yl}carbonyl)cyclopentyl]-3-methoxytetrahydro-2H-pyran-4-amine (19). After evaluation in 28-day toxicology studies, compound 19 (INCB10820/PF-4178903) was selected as a clinical candidate.

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