Discovery of Biaryl Amides as Potent, Orally Bioavailable, and CNS Penetrant ROR纬t Inhibitors

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• 作者：Yonghui Wang ; Wei Cai ; Yaobang Cheng ; Ting Yang ; Qian Liu ; Guifeng Zhang ; Qinghua Meng ; Fangbin Han ; Yafei Huang ; Ling Zhou ; Zhijun Xiang ; Yong-Gang Zhao ; Yan Xu ; Ziqiang Cheng ; Sijie Lu ; Qianqian Wu ; Jia-Ning Xiang ; John D. Elliott ; Stewart Leung ; Feng Ren ; Xichen Lin
• 刊名：ACS Medicinal Chemistry Letters
• 出版年：2015
• 出版时间：July 9, 2015
• 年：2015
• 卷：6
• 期：7
• 页码：787-792
• 全文大小：394K
• ISSN：1948-5875

文摘

A novel series of biaryl amides was identified as ROR纬t inhibitors through core replacement of a starting hit 1. Structure鈥揳ctivity relationship exploration on the biaryl moiety led to discovery of potent ROR纬t 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.