2. Academic Validation
  3. Discovery of INCB8761/PF-4136309, a Potent, Selective, and Orally Bioavailable CCR2 Antagonist

Discovery of INCB8761/PF-4136309, a Potent, Selective, and Orally Bioavailable CCR2 Antagonist

  • ACS Med Chem Lett. 2011 Oct 5;2(12):913-8. doi: 10.1021/ml200199c.
Chu-Biao Xue 1,  Anlai Wang 1,  Qi Han 1,  Yingxin Zhang 1,  Ganfeng Cao 1,  Hao Feng 1,  Taisheng Huang 1,  Changsheng Zheng 1,  Michael Xia 1,  Ke Zhang 1,  Lingquan Kong 1,  Joseph Glenn 1,  Rajan Anand 1,  David Meloni 1,  D J Robinson 1,  Lixin Shao 1,  Lou Storace 1,  Mei Li 1,  Robert O Hughes 2,  Rajesh Devraj 2,  Philip A Morton 2,  D Joseph Rogier 2,  Maryanne Covington 1,  Peggy Scherle 1,  Sharon Diamond 1,  Tom Emm 1,  Swamy Yeleswaram 1,  Nancy Contel 1,  Kris Vaddi 1,  Robert Newton 1,  Greg Hollis 1,  Brian Metcalf 1
Affiliations

Affiliations

  • 1 Incyte Corporation , Experimental Station E336, Wilmington, Delaware 19880, United States.
  • 2 Pfizer Global Research and Development , Chesterfield Parkway West, St. Louis, Missouri 63017, United States.
PMID: 24900280 DOI: 10.1021/ml200199c
Abstract

We report the discovery of a new (S)-3-aminopyrrolidine series of CCR2 antagonists. Structure-activity relationship studies on this new series led to the identification of 17 (INCB8761/PF-4136309) that exhibited potent CCR2 antagonistic activity, high selectivity, weak hERG activity, and an excellent in vitro and in vivo ADMET profile. INCB8761/PF-4136309 has entered human clinical trials.

Keywords

CCR2; antagonist; chemokine; hERG.

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