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Discovery and biological evaluation of novel G protein‐coupled receptor 119 agonists for type 2 diabetes
Author(s) -
Zhou Ying,
Wang Youzhi,
Zhang Leilei,
Tang Chunlei,
Feng Bainian
Publication year - 2019
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201800267
Subject(s) - potency , agonist , chemistry , g protein coupled receptor , receptor , in vitro , pharmacology , type 2 diabetes mellitus , type 2 diabetes , diabetes mellitus , biological activity , biochemistry , endocrinology , medicine
Abstract G protein‐coupled receptor 119 (GPR119) is a member of the GPCR family promising to be the target for type 2 diabetes mellitus (T2DM) treatment. In this work, 30 novel compounds were designed, synthesized, and evaluated by in vitro cAMP activation assay, where compounds II–14 and II–18 showed the best potency with EC 50 values of 69 and 99 nM, respectively. In the oral glucose tolerance test, compound II–18 showed even more efficacious activity in lowering blood excursions than MBX‐2982 at a fixed dose of 30 mg/kg. Here, we report that compound II–18 with its excellent agonistic activity and its orally effective activity in decreasing blood glucose deviations may serve as a potent GPR119 agonist for the treatment of T2DM.