Discovery of Chromane Propionic Acid Analogues as Selective Agonists of GPR120 with in Vivo Activity in Rodents

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• 作者：Gregory L. AdamsFrancisco Velazquez ; Charles Jayne ; Unmesh Shah ; Shouwu Miao ; Eric R. Ashley ; Maria MadeiraTaro E. Akiyama ; Jerry Di Salvo ; Takao Suzuki ; Nengxue Wang ; Quang Truong ; Eric Gilbert ; Dan Zhou ; Andreas Verras ; Melissa Kirkland ; Michele Pachanski ; Maryann Powles ; Wu Yin ; Feroze Ujjainwalla ; Srikanth Venkatraman ; Scott D. Edmondson
• 刊名：ACS Medicinal Chemistry Letters
• 出版年：2017
• 出版时间：January 12, 2017
• 年：2017
• 卷：8
• 期：1
• 页码：96-101
• 全文大小：482K
• ISSN：1948-5875

文摘

GPR120 (FFAR4) is a fatty acid sensing G protein coupled receptor (GPCR) that has been identified as a target for possible treatment of type 2 diabetes. A selective activator of GPR120 containing a chromane scaffold has been designed, synthesized, and evaluated in vivo. Results of these efforts suggest that chromane propionic acid 18 is a suitable tool molecule for further animal studies. Compound 18 is selective over the closely related target GPR40 (FFAR1), has a clean off-target profile, demonstrates suitable pharmacokinetic properties, and has been evaluated in wild-type/knockout GPR120 mouse oGTT studies.