Design, synthesis and evaluation of 1-benzyl-1H-imidazole-5-carboxamide derivatives as potent TGR5 agonists,Bioorganic & Medicinal Chemistry

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Design, synthesis and evaluation of 1-benzyl-1H-imidazole-5-carboxamide derivatives as potent TGR5 agonists
Bioorganic & Medicinal Chemistry ( IF 3.3 ) Pub Date : 2020-12-27 , DOI: 10.1016/j.bmc.2020.115972
Shizhen Zhao ₁ , Xinping Li ₁ , Le Wang ₁ , Wenjing Peng ₁ , Wenling Ye ₁ , Weiguo Li ₁ , Yan-Dong Wang ₂ , Wei-Dong Chen ₃

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TGR5 is emerging as an important and promising target for the treatment of diabetes, obesity and other metabolic syndromes. A series of novel 1-benzyl-1H-imidazole-5-carboxamide derivatives was designed, synthesized and evaluated in vitro and in vivo. The most potent compounds 19d and 19e exhibited excellent agonistic activities against hTGR5, which was superior to those of the reference drugs INT-777 and LCA. In addition, compounds 19d and 19e exhibited good selectivity against FXR and presented significant glucose-lowering effects in vivo. Compound 19d could stimulate GLP-1 secretion by activating of TGR5.

中文翻译：

设计、合成和评价作为有效 TGR5 激动剂的 1-benzyl-1H-imidazole-5-carboxamide 衍生物

TGR5 正在成为治疗糖尿病、肥胖症和其他代谢综合征的重要且有前景的靶点。一系列新的 1-benzyl-1 H -imidazole-5-carboxamide 衍生物被设计、合成和体外和体内评估。最有效的化合物19d和19e对 hTGR5 表现出优异的激动活性，优于参考药物 INT-777 和 LCA。此外，化合物19d和19e对FXR表现出良好的选择性，并在体内表现出显着的降糖作用。化合物19d可以通过激活TGR5来刺激GLP-1分泌。

更新日期：2021-01-10

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