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Microwave-Assisted Preparation of 1-Aryl-1H-pyrazole-5-amines
Published on: June 23, 2019
Design, synthesis and evaluation of 3-phenoxypyrazine-2-carboxamide derivatives as potent TGR5 agonists
Shizhen Zhao1, Le Wang1, Jie Wang1
1Key Laboratory of Receptors-Mediated Gene Regulation and Drug Discovery, Hebei Key Laboratory of Liver Disease, People's Hospital of Hebei, School of Medicine, Henan University Kaifeng China dr_rfhou@126.com dongbinyang@126.com.
Abstract:
TGR5 is emerging as an important and promising target for the treatment of non-alcoholic steatohepatitis, type 2 diabetes mellitus (T2DM), and obesity. A series of novel 3-phenoxypyrazine-2-carboxamide derivatives were designed, synthesized and evaluated in vitro and in vivo. The most potent compounds 18g and 18k exhibited excellent hTGR5 agonist activity, which was superior to those of the reference drug INT-777. In addition, compound 18k could significantly reduce blood glucose levels in C57 BL/6 mice and stimulate GLP-1 secretion in NCI-H716 cells and C57 BL/6 mice.
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