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SAR Studies of Indole-5-propanoic Acid Derivatives To Develop Novel GPR40 Agonists.

ABSTRACT: G-protein coupled receptor 40 (GPR40) has been considered to be an attractive drug target for the treatment of type 2 diabetes because of its role in free fatty acids-mediated enhancement of glucose-stimulated insulin secretion (GSIS) from pancreatic ?-cells. A series of indole-5-propanoic acid compounds were synthesized, and their GPR40 agonistic activities were evaluated by nuclear factor of activated T-cells reporter assay and GSIS assay in the MIN-6 insulinoma cells. Three compounds, 8h (EC50 = 58.6 nM), 8i (EC50 = 37.8 nM), and 8o (EC50 = 9.4 nM), were identified as potent GPR40 agonists with good GSIS effects.

SUBMITTER: Yoon DO

PROVIDER: S-EPMC5733302 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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SAR Studies of Indole-5-propanoic Acid Derivatives To Develop Novel GPR40 Agonists.

Yoon Dong-Oh DO Zhao Xiaodi X Son Dohyun D Han Jung Tae JT Yun Jaesook J Shin Dongyun D Park Hyun-Ju HJ

ACS medicinal chemistry letters 20171121 12

G-protein coupled receptor 40 (GPR40) has been considered to be an attractive drug target for the treatment of type 2 diabetes because of its role in free fatty acids-mediated enhancement of glucose-stimulated insulin secretion (GSIS) from pancreatic β-cells. A series of indole-5-propanoic acid compounds were synthesized, and their GPR40 agonistic activities were evaluated by nuclear factor of activated T-cells reporter assay and GSIS assay in the MIN-6 insulinoma cells. Three compounds, <b>8h</ ...[more]

PMID: 29259758

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