Discovery of 2H-Chromen-2-one Derivatives as G Protein-Coupled Receptor-35 Agonists

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• 作者：Lai Wei ; Jixia Wang ; Xiuli Zhang ; Ping Wang ; Yaopeng Zhao ; Jiaqi Li ; Tao Hou ; Lala Qu ; Liying Shi ; Xinmiao LiangYe Fang
• 刊名：Journal of Medicinal Chemistry
• 出版年：2017
• 出版时间：January 12, 2017
• 年：2017
• 卷：60
• 期：1
• 页码：362-372
• 全文大小：563K
• ISSN：1520-4804

文摘

A family of 2H-chromen-2-one derivatives were identified as G protein-coupled receptor-35 (GPR35) agonists using dynamic mass redistribution assays in HT-29 cells. The compounds with 1H-tetrazol-5-yl in 3-substituted position displayed higher potency than the corresponding carboxyl analogs, and the hydroxyl group in the 7-position also played an important role in GPR35 agonistic activity. 6-Bromo-7-hydroxy-8-nitro-3-(1H-tetrazol-5-yl)-2H-chromen-2-one (50) was found to be the most potent GPR35 agonist with an EC₅₀ of 5.8 nM. Calculating the physicochemical properties of compounds with moderate to high potency suggested that compounds 30, 50, and 51 showed good druggability. This study provides a novel series of GPR35 agonists, and compound 50 may be a powerful tool to study GPR35.