Discovery of Biaryl Amides as Potent, Orally Bioavailable, and CNS Penetrant RORγt Inhibitors
Discovery of Biaryl Amides as Potent, Orally Bioavailable, and CNS Penetrant RORγt Inhibitors
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DOI：
10.1021/acsmedchemlett.5b00122
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发表时间：
2015-07-01
影响因子：
4.2
通讯作者：
Lin, Xichen
中科院分区：
文献类型：
--
作者：
Wang, Yonghui;Cai, Wei;Lin, Xichen
一系列新的联芳基酰胺通过起始命中1的核心置换被鉴定为ROR γ t抑制剂。对联芳基部分的结构活性关系探索导致发现具有良好口服生物利用度和CNS渗透性的有效ROR γ t抑制剂。化合物9a和9g在EAE小鼠中表现出优异的体内功效，每日一次口服给药具有剂量依赖性。
A novel series of biaryl amides was identified as ROR gamma t inhibitors through core replacement of a starting hit 1. Structure activity relationship exploration on the biaryl moiety led to discovery of potent ROR gamma 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.