title: Discovery of INCB8761/PF-4136309, a Potent, Selective, and Orally Bioavailable CCR2 Antagonist.
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.
authors.affiliation: Incyte Corporation , Experimental Station E336, Wilmington, Delaware 19880, United States.
authors.forename: Chu-Biao
authors.initials: CB
authors.lastname: Xue
authors.affiliation: Incyte Corporation , Experimental Station E336, Wilmington, Delaware 19880, United States.
authors.forename: Anlai
authors.initials: A
authors.lastname: Wang
authors.affiliation: Incyte Corporation , Experimental Station E336, Wilmington, Delaware 19880, United States.
authors.forename: Qi
authors.initials: Q
authors.lastname: Han
authors.affiliation: Incyte Corporation , Experimental Station E336, Wilmington, Delaware 19880, United States.
authors.forename: Yingxin
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Incyte Corporation , Experimental Station E336, Wilmington, Delaware 19880, United States.
authors.forename: Ganfeng
authors.initials: G
authors.lastname: Cao
authors.affiliation: Incyte Corporation , Experimental Station E336, Wilmington, Delaware 19880, United States.
authors.forename: Hao
authors.initials: H
authors.lastname: Feng
authors.affiliation: Incyte Corporation , Experimental Station E336, Wilmington, Delaware 19880, United States.
authors.forename: Taisheng
authors.initials: T
authors.lastname: Huang
authors.affiliation: Incyte Corporation , Experimental Station E336, Wilmington, Delaware 19880, United States.
authors.forename: Changsheng
authors.initials: C
authors.lastname: Zheng
authors.affiliation: Incyte Corporation , Experimental Station E336, Wilmington, Delaware 19880, United States.
authors.forename: Michael
authors.initials: M
authors.lastname: Xia
authors.affiliation: Incyte Corporation , Experimental Station E336, Wilmington, Delaware 19880, United States.
authors.forename: Ke
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Incyte Corporation , Experimental Station E336, Wilmington, Delaware 19880, United States.
authors.forename: Lingquan
authors.initials: L
authors.lastname: Kong
authors.affiliation: Incyte Corporation , Experimental Station E336, Wilmington, Delaware 19880, United States.
authors.forename: Joseph
authors.initials: J
authors.lastname: Glenn
authors.affiliation: Incyte Corporation , Experimental Station E336, Wilmington, Delaware 19880, United States.
authors.forename: Rajan
authors.initials: R
authors.lastname: Anand
authors.affiliation: Incyte Corporation , Experimental Station E336, Wilmington, Delaware 19880, United States.
authors.forename: David
authors.initials: D
authors.lastname: Meloni
authors.affiliation: Incyte Corporation , Experimental Station E336, Wilmington, Delaware 19880, United States.
authors.forename: D J
authors.initials: DJ
authors.lastname: Robinson
authors.affiliation: Incyte Corporation , Experimental Station E336, Wilmington, Delaware 19880, United States.
authors.forename: Lixin
authors.initials: L
authors.lastname: Shao
authors.affiliation: Incyte Corporation , Experimental Station E336, Wilmington, Delaware 19880, United States.
authors.forename: Lou
authors.initials: L
authors.lastname: Storace
authors.affiliation: Incyte Corporation , Experimental Station E336, Wilmington, Delaware 19880, United States.
authors.forename: Mei
authors.initials: M
authors.lastname: Li
authors.affiliation: Pfizer Global Research and Development , Chesterfield Parkway West, St. Louis, Missouri 63017, United States.
authors.forename: Robert O
authors.initials: RO
authors.lastname: Hughes
authors.affiliation: Pfizer Global Research and Development , Chesterfield Parkway West, St. Louis, Missouri 63017, United States.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Devraj
authors.affiliation: Pfizer Global Research and Development , Chesterfield Parkway West, St. Louis, Missouri 63017, United States.
authors.forename: Philip A
authors.initials: PA
authors.lastname: Morton
authors.affiliation: Pfizer Global Research and Development , Chesterfield Parkway West, St. Louis, Missouri 63017, United States.
authors.forename: D Joseph
authors.initials: DJ
authors.lastname: Rogier
authors.affiliation: Incyte Corporation , Experimental Station E336, Wilmington, Delaware 19880, United States.
authors.forename: Maryanne
authors.initials: M
authors.lastname: Covington
authors.affiliation: Incyte Corporation , Experimental Station E336, Wilmington, Delaware 19880, United States.
authors.forename: Peggy
authors.initials: P
authors.lastname: Scherle
authors.affiliation: Incyte Corporation , Experimental Station E336, Wilmington, Delaware 19880, United States.
authors.forename: Sharon
authors.initials: S
authors.lastname: Diamond
authors.affiliation: Incyte Corporation , Experimental Station E336, Wilmington, Delaware 19880, United States.
authors.forename: Tom
authors.initials: T
authors.lastname: Emm
authors.affiliation: Incyte Corporation , Experimental Station E336, Wilmington, Delaware 19880, United States.
authors.forename: Swamy
authors.initials: S
authors.lastname: Yeleswaram
authors.affiliation: Incyte Corporation , Experimental Station E336, Wilmington, Delaware 19880, United States.
authors.forename: Nancy
authors.initials: N
authors.lastname: Contel
authors.affiliation: Incyte Corporation , Experimental Station E336, Wilmington, Delaware 19880, United States.
authors.forename: Kris
authors.initials: K
authors.lastname: Vaddi
authors.affiliation: Incyte Corporation , Experimental Station E336, Wilmington, Delaware 19880, United States.
authors.forename: Robert
authors.initials: R
authors.lastname: Newton
authors.affiliation: Incyte Corporation , Experimental Station E336, Wilmington, Delaware 19880, United States.
authors.forename: Greg
authors.initials: G
authors.lastname: Hollis
authors.affiliation: Incyte Corporation , Experimental Station E336, Wilmington, Delaware 19880, United States.
authors.forename: Brian
authors.initials: B
authors.lastname: Metcalf
keywords: CCR2; antagonist; chemokine; hERG