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

ABSTRACT: 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.

SUBMITTER: Adams GL

PROVIDER: S-EPMC5238488 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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

Adams Gregory L GL Velazquez Francisco F Jayne Charles C Shah Unmesh U Miao Shouwu S Ashley Eric R ER Madeira Maria M Akiyama Taro E TE Di Salvo Jerry J Suzuki Takao T Wang Nengxue N Truong Quang Q Gilbert Eric E Zhou Dan D Verras Andreas A Kirkland Melissa M Pachanski Michele M Powles Maryann M Yin Wu W Ujjainwalla Feroze F Venkatraman Srikanth S Edmondson Scott D SD

ACS medicinal chemistry letters 20161206 1

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 ...[more]

PMID: 28105282

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