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 EC50 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.
Keywords: GPR119; agonistic activity; biological evaluation; synthesis; type 2 diabetes.
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