Chengdu Grain Storage Research Institute of SinoGrain, Cereals and Oils Inspection Center, Chengdu, China.
Division of Nephrology, Kidney Research Institute, West China Hospital, West China Medical School Sichuan University, Chengdu, 610041, China.
Mol Divers. 2017 Aug;21(3):637-654. doi: 10.1007/s11030-017-9755-6. Epub 2017 Jun 27.
A series of fused-pyrimidine derivatives were prepared and evaluated for their agonistic activities against human GPR119. Compound 9i showed high potent agonistic activity against HEK293T cells over-expressing human GPR119 and improved glucose tolerance in dose-dependent manner, as well as promoted insulin secretion. In a DIO mice model, 9i also ameliorated the obese-related symptoms by decreasing the body weights without markedly changing food intake, normalized some serum biomarkers, such as ALT, AST, ALP, GLU, CHOL, HDL, and LDL, and exerted therapeutic activity on fat deposition in liver tissue. We consider 9i to have utility as a GPR119 agonists for the treatment of type 2 diabetes mellitus and obese-related symptoms.
一系列的嘧啶融合衍生物被制备并评估其对人源 GPR119 的激动活性。化合物 9i 对过表达人源 GPR119 的 HEK293T 细胞显示出高的激动活性，并以剂量依赖性方式改善葡萄糖耐量，同时促进胰岛素分泌。在 DIO 小鼠模型中，9i 通过降低体重而不显著改变食物摄入来改善肥胖相关症状，使一些血清生物标志物（如 ALT、AST、ALP、GLU、CHOL、HDL 和 LDL）正常化，并对肝组织中的脂肪沉积发挥治疗作用。我们认为 9i 可用作 GPR119 激动剂，用于治疗 2 型糖尿病和肥胖相关症状。
