Design and biological evaluation of tetrahydropyridine derivatives as novel human GPR119 agonists.
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Zuo Z, Chen M, Shao X, Qian X, Liu X, Zhou X, Xiang J, Deng P, Li Y, Jie H, Liu C, Cen X, Xie Y, Zhao Y
Design and biological evaluation of tetrahydropyridine derivatives as novel human GPR119 agonists.
Bioorg Med Chem Lett. 2020 Feb 15;30(4):126855. doi: 10.1016/j.bmcl.2019.126855. Epub 2019 Dec 3.
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- 31898998 [ View in PubMed]
- Abstract
A series of novel tetrahydropyridine derivatives were prepared and evaluated using cell-based measurements. Systematic optimization of general structure G-1 led to the identification of compound 35 (EC(50) = 4.9 nM) and 37 (EC(50) = 8.8 nM) with high GPR119 agonism activity and moderate clog P. Through single and long-term pharmacodynamic experiments, we found that compound35 showed a hypoglycemic effect and may have an effect on improving basal metabolic rate in DIO mice. Both in vitro and in vivo tests indicated that compound 35 was a potential potent GPR119 agonist in allusion to T2DM treatment.