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Design, synthesis and evaluation of 3-phenoxypyrazine-2-carboxamide derivatives as potent TGR5 agonists.

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.

SUBMITTER: Zhao S

PROVIDER: S-EPMC8979340 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Design, synthesis and evaluation of 3-phenoxypyrazine-2-carboxamide derivatives as potent TGR5 agonists.

Zhao Shizhen S Wang Le L Wang Jie J Wang Chenwei C Zheng Shaowei S Fu Yajie Y Li Yunfu Y Chen Wei-Dong WD Chen Wei-Dong WD Hou Ruifang R Yang Dongbin D Wang Yan-Dong YD

RSC advances 20220127 6

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 <i>in vitro</i> and <i>in vivo</i>. 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 l ...[more]

PMID: 35425398

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