Discovery of Tertiary Amine and Indole Derivatives as Potent ROR gamma t Inverse Agonists

作者：Yang Ting; Liu Qian; Cheng Yaobang; Cai Wei; Ma Yingli; Yang Liuqing; Wu Qianqian; Orband Miller Lisa A; Zhou Ling; Xiang Zhijun; Huxdorf Melanie; Zhang Wei; Zhang Jing; Xiang Jia Ning; Leung Stewart; Qiu Yang; Zhong Zhong; Elliott John D; Lin Xichen; Wang Yonghui^*

来源：ACS Medicinal Chemistry Letters, 2014, 5(1): 65-68.

DOI：10.1021/ml4003875

• ROR gamma t
• agonists
• inverse agonists
• Th17 cell differentiation
• cocrystal structure
• structure-based design

A novel series of tertiary amines as retinoid-related orphan receptor gamma-t (ROR gamma t) inverse agonists was discovered through agonist/inverse agonist conversion. The level of ROR gamma t inhibition can be enhanced by modulating the conformational disruption of H12 in ROR gamma t LBD. Linker exploration and rational design led to the discovery of more potent indole-based ROR gamma t inverse agonists.

• 出版日期2014-1