title: Discovery of INCB9471, a Potent, Selective, and Orally Bioavailable CCR5 Antagonist with Potent Anti-HIV-1 Activity.
abstract: To identify a CCR5 antagonist as an HIV-1 entry inhibitor, we designed a novel series of indane derivatives based on conformational considerations. Modification on the indane ring led to the discovery of compound 22a (INCB9471) that exhibited high affinity for CCR5, potent anti-HIV-1 activity, high receptor selectivity, excellent oral bioavailability, and a tolerated safety profile. INCB9471 has entered human clinical trials.
authors.affiliation: Incyte Corporation, Experimental Station E336, Wilmington, Delaware 19880.
authors.forename: Chu-Biao
authors.initials: CB
authors.lastname: Xue
authors.affiliation: Incyte Corporation, Experimental Station E336, Wilmington, Delaware 19880.
authors.forename: Lihua
authors.initials: L
authors.lastname: Chen
authors.affiliation: Incyte Corporation, Experimental Station E336, Wilmington, Delaware 19880.
authors.forename: Ganfeng
authors.initials: G
authors.lastname: Cao
authors.affiliation: Incyte Corporation, Experimental Station E336, Wilmington, Delaware 19880.
authors.forename: Ke
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Incyte Corporation, Experimental Station E336, Wilmington, Delaware 19880.
authors.forename: Anlai
authors.initials: A
authors.lastname: Wang
authors.affiliation: Incyte Corporation, Experimental Station E336, Wilmington, Delaware 19880.
authors.forename: David
authors.initials: D
authors.lastname: Meloni
authors.affiliation: Incyte Corporation, Experimental Station E336, Wilmington, Delaware 19880.
authors.forename: Joseph
authors.initials: J
authors.lastname: Glenn
authors.affiliation: Incyte Corporation, Experimental Station E336, Wilmington, Delaware 19880.
authors.forename: Rajan
authors.initials: R
authors.lastname: Anand
authors.affiliation: Incyte Corporation, Experimental Station E336, Wilmington, Delaware 19880.
authors.forename: Michael
authors.initials: M
authors.lastname: Xia
authors.affiliation: Incyte Corporation, Experimental Station E336, Wilmington, Delaware 19880.
authors.forename: Ling
authors.initials: L
authors.lastname: Kong
authors.affiliation: Incyte Corporation, Experimental Station E336, Wilmington, Delaware 19880.
authors.forename: Taisheng
authors.initials: T
authors.lastname: Huang
authors.affiliation: Incyte Corporation, Experimental Station E336, Wilmington, Delaware 19880.
authors.forename: Hao
authors.initials: H
authors.lastname: Feng
authors.affiliation: Incyte Corporation, Experimental Station E336, Wilmington, Delaware 19880.
authors.forename: Changsheng
authors.initials: C
authors.lastname: Zheng
authors.affiliation: Incyte Corporation, Experimental Station E336, Wilmington, Delaware 19880.
authors.forename: Mei
authors.initials: M
authors.lastname: Li
authors.affiliation: Incyte Corporation, Experimental Station E336, Wilmington, Delaware 19880.
authors.forename: Laurine
authors.initials: L
authors.lastname: Galya
authors.affiliation: Incyte Corporation, Experimental Station E336, Wilmington, Delaware 19880.
authors.forename: Jiacheng
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Incyte Corporation, Experimental Station E336, Wilmington, Delaware 19880.
authors.forename: Niu
authors.initials: N
authors.lastname: Shin
authors.affiliation: Incyte Corporation, Experimental Station E336, Wilmington, Delaware 19880.
authors.forename: Fredric
authors.initials: F
authors.lastname: Baribaud
authors.affiliation: Incyte Corporation, Experimental Station E336, Wilmington, Delaware 19880.
authors.forename: Kim
authors.initials: K
authors.lastname: Solomon
authors.affiliation: Incyte Corporation, Experimental Station E336, Wilmington, Delaware 19880.
authors.forename: Peggy
authors.initials: P
authors.lastname: Scherle
authors.affiliation: Incyte Corporation, Experimental Station E336, Wilmington, Delaware 19880.
authors.forename: Bitao
authors.initials: B
authors.lastname: Zhao
authors.affiliation: Incyte Corporation, Experimental Station E336, Wilmington, Delaware 19880.
authors.forename: Sharon
authors.initials: S
authors.lastname: Diamond
authors.affiliation: Incyte Corporation, Experimental Station E336, Wilmington, Delaware 19880.
authors.forename: Tom
authors.initials: T
authors.lastname: Emm
authors.affiliation: Incyte Corporation, Experimental Station E336, Wilmington, Delaware 19880.
authors.forename: Douglas
authors.initials: D
authors.lastname: Keller
authors.affiliation: Incyte Corporation, Experimental Station E336, Wilmington, Delaware 19880.
authors.forename: Nancy
authors.initials: N
authors.lastname: Contel
authors.affiliation: Incyte Corporation, Experimental Station E336, Wilmington, Delaware 19880.
authors.forename: Swamy
authors.initials: S
authors.lastname: Yeleswaram
authors.affiliation: Incyte Corporation, Experimental Station E336, Wilmington, Delaware 19880.
authors.forename: Kris
authors.initials: K
authors.lastname: Vaddi
authors.affiliation: Incyte Corporation, Experimental Station E336, Wilmington, Delaware 19880.
authors.forename: Gregory
authors.initials: G
authors.lastname: Hollis
authors.affiliation: Incyte Corporation, Experimental Station E336, Wilmington, Delaware 19880.
authors.forename: Robert
authors.initials: R
authors.lastname: Newton
authors.affiliation: Incyte Corporation, Experimental Station E336, Wilmington, Delaware 19880.
authors.forename: Steven
authors.initials: S
authors.lastname: Friedman
authors.affiliation: Incyte Corporation, Experimental Station E336, Wilmington, Delaware 19880.
authors.forename: Brian
authors.initials: B
authors.lastname: Metcalf
keywords: CCR5; HIV-1; antagonist; antiviral; coreceptor