Zydus Research Centre, Cadila Healthcare Ltd., Sarkhej-Bavla N.H. No. 8 A, Moraiya, Ahmedabad 382 210, India.
Zydus Research Centre, Cadila Healthcare Ltd., Sarkhej-Bavla N.H. No. 8 A, Moraiya, Ahmedabad 382 210, India; Chemistry Department, The M. S. University, Baroda 390 002, India.
Bioorg Med Chem Lett. 2018 Jun 1;28(10):1849-1852. doi: 10.1016/j.bmcl.2018.04.011. Epub 2018 Apr 5.
TGR5 is a member of G protein-coupled receptor (GPCR) superfamily, a promising molecular target for metabolic diseases. Activation of TGR5 promotes secretion of glucagon-like peptide-1 (GLP-1), which activates insulin secretion. A series of 2-thio-imidazole derivatives have been identified as novel, potent and orally efficacious TGR5 agonists. Compound 4d, a novel TGR5 agonist, in combination with Sitagliptin, a DPP-4 inhibitor, has demonstrated an adequate GLP-1 secretion and glucose lowering effect in animal models, suggesting a potential clinical option in treatment of type-2 diabetes.
TGR5 是 G 蛋白偶联受体（GPCR）超家族的一员，是代谢性疾病有前途的分子靶标。TGR5 的激活促进胰高血糖素样肽-1（GLP-1）的分泌，从而激活胰岛素分泌。一系列 2-硫代咪唑衍生物已被鉴定为新型、有效和口服有效的 TGR5 激动剂。新型 TGR5 激动剂 4d 与 DPP-4 抑制剂西他列汀联合使用，在动物模型中显示出足够的 GLP-1 分泌和降血糖作用，这表明它可能是治疗 2 型糖尿病的一种临床选择。
