Design, synthesis and evaluation of 1-benzyl-1H-imidazole-5-carboxamide derivatives as potent TGR5 agonists.

Basic Information

ID: ALA4680349

Journal: Bioorg Med Chem

Title: Design, synthesis and evaluation of 1-benzyl-1H-imidazole-5-carboxamide derivatives as potent TGR5 agonists.

Authors: Zhao S,Li X,Wang L,Peng W,Ye W,Li W,Wang YD,Chen WD

Abstract: 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.

CiteXplore: 33440321

DOI: 10.1016/j.bmc.2020.115972

Patent ID: