title: Discovery of Biaryl Amides as Potent, Orally Bioavailable, and CNS Penetrant RORγt Inhibitors.
abstract: A novel series of biaryl amides was identified as RORγt inhibitors through core replacement of a starting hit 1. Structure-activity relationship exploration on the biaryl moiety led to discovery of potent RORγt inhibitors with good oral bioavailability and CNS penetration. Compounds 9a and 9g demonstrated excellent in vivo efficacy in EAE mice dose dependently with once daily oral administration.
authors.affiliation: School of Pharmacy, Fudan University , 826 Zhangheng Road, Pudong, Shanghai 201203, China.
authors.forename: Yonghui
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Research and Development, GlaxoSmithKline , No. 3 Building, 898 Halei Road, Pudong, Shanghai 201203, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Cai
authors.affiliation: Research and Development, GlaxoSmithKline , No. 3 Building, 898 Halei Road, Pudong, Shanghai 201203, China.
authors.forename: Yaobang
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Research and Development, GlaxoSmithKline , No. 3 Building, 898 Halei Road, Pudong, Shanghai 201203, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Yang
authors.affiliation: Research and Development, GlaxoSmithKline , No. 3 Building, 898 Halei Road, Pudong, Shanghai 201203, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Research and Development, GlaxoSmithKline , No. 3 Building, 898 Halei Road, Pudong, Shanghai 201203, China.
authors.forename: Guifeng
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Research and Development, GlaxoSmithKline , No. 3 Building, 898 Halei Road, Pudong, Shanghai 201203, China.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Meng
authors.affiliation: Research and Development, GlaxoSmithKline , No. 3 Building, 898 Halei Road, Pudong, Shanghai 201203, China.
authors.forename: Fangbin
authors.initials: F
authors.lastname: Han
authors.affiliation: School of Pharmacy, Fudan University , 826 Zhangheng Road, Pudong, Shanghai 201203, China.
authors.forename: Yafei
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Research and Development, GlaxoSmithKline , No. 3 Building, 898 Halei Road, Pudong, Shanghai 201203, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Research and Development, GlaxoSmithKline , No. 3 Building, 898 Halei Road, Pudong, Shanghai 201203, China.
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Xiang
authors.affiliation: Research and Development, GlaxoSmithKline , No. 3 Building, 898 Halei Road, Pudong, Shanghai 201203, China.
authors.forename: Yong-Gang
authors.initials: YG
authors.lastname: Zhao
authors.affiliation: Research and Development, GlaxoSmithKline , No. 3 Building, 898 Halei Road, Pudong, Shanghai 201203, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Research and Development, GlaxoSmithKline , No. 3 Building, 898 Halei Road, Pudong, Shanghai 201203, China.
authors.forename: Ziqiang
authors.initials: Z
authors.lastname: Cheng
authors.affiliation: Research and Development, GlaxoSmithKline , No. 3 Building, 898 Halei Road, Pudong, Shanghai 201203, China.
authors.forename: Sijie
authors.initials: S
authors.lastname: Lu
authors.affiliation: Research and Development, GlaxoSmithKline , No. 3 Building, 898 Halei Road, Pudong, Shanghai 201203, China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Research and Development, GlaxoSmithKline , No. 3 Building, 898 Halei Road, Pudong, Shanghai 201203, China.
authors.forename: Jia-Ning
authors.initials: JN
authors.lastname: Xiang
authors.affiliation: Research and Development, GlaxoSmithKline , No. 3 Building, 898 Halei Road, Pudong, Shanghai 201203, China.
authors.forename: John D
authors.initials: JD
authors.lastname: Elliott
authors.affiliation: Research and Development, GlaxoSmithKline , No. 3 Building, 898 Halei Road, Pudong, Shanghai 201203, China.
authors.forename: Stewart
authors.initials: S
authors.lastname: Leung
authors.affiliation: Research and Development, GlaxoSmithKline , No. 3 Building, 898 Halei Road, Pudong, Shanghai 201203, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Ren
authors.affiliation: Research and Development, GlaxoSmithKline , No. 3 Building, 898 Halei Road, Pudong, Shanghai 201203, China.
authors.forename: Xichen
authors.initials: X
authors.lastname: Lin
keywords: EAE; RORγt inhibitor; Th17 cell differentiation; biaryl amides; multiple sclerosis