| Literature DB >> 26277758 |
Yonghui Wang1, Ting Yang2, Qian Liu2, Yingli Ma2, Liuqing Yang2, Ling Zhou2, Zhijun Xiang2, Ziqiang Cheng2, Sijie Lu2, Lisa A Orband-Miller2, Wei Zhang2, Qianqian Wu2, Kathleen Zhang2, Yi Li2, Jia-Ning Xiang2, John D Elliott2, Stewart Leung2, Feng Ren2, Xichen Lin3.
Abstract
A novel series of N-(4-aryl-5-aryloxy-thiazol-2-yl)-amides as RORγt inverse agonists was discovered. Binding mode analysis of a RORγt partial agonist (2c) revealed by co-crystal structure in RORγt LBD suggests that the inverse agonists do not directly interfere with the interaction between H12 and the RORγt LBD. Detailed SAR exploration led to identification of potent RORγt inverse agonists such as 3m with a pIC50 of 8.0. Selected compounds in the series showed reasonable activity in Th17 cell differentiation assay as well as low intrinsic clearance in mouse liver microsomes.Entities:
Keywords: Crystal structure; RORγt inverse agonists; Th17 cell differentiation; Thiazole ether amides
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Year: 2015 PMID： 26277758 DOI： 10.1016/j.bmc.2015.07.068
Source DB: PubMed Journal: Bioorg Med Chem ISSN： 0968-0896 Impact factor: 3.641