期刊
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
卷 36, 期 -, 页码 -出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2021.127786
关键词
Nuclear receptor; RORγ t; Inverse agonist
The study focused on ROR gamma t, a potential therapeutic target for immune diseases, and successfully identified a compound with potent inhibitory activity and favorable pharmacokinetic properties through structure-activity relationship studies.
The retinoic acid receptor-related orphan nuclear receptor gamma t (ROR gamma t), which is a promising therapeutic target for immune diseases, is a major transcription factor of genes related to psoriasis pathogenesis, such as interleukin (IL)-17A, IL-22, and IL-23R. Inspired by the co-crystal structure of ROR gamma t, a 6-oxo-4-phenyl-hexanoic acid derivative 6a was designed, synthesized, and identified as a ligand of ROR gamma t. The structure-activity relationship (SAR) studies in 6a, which focus on the improvement of its membrane permeability profile by introducing chlorine atoms, led to finding 12a, which has a potent ROR gamma t inhibitory activity and a favorable pharmacokinetic profile.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据