Unknown

Dataset Information

0

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

Json Xml
altmetric image

Publications

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]

Similar Datasets

Unknown Synthesis and Evaluation of Thiazolyl-indole-2-carboxamide Derivatives as Potent Multitarget Anticancer Agents.
| S-EPMC11465279 | biostudies-literature
Unknown Design, Synthesis, and Bioactivity Evaluation of New Thiochromanone Derivatives Containing a Carboxamide Moiety.
| S-EPMC8348251 | biostudies-literature
Unknown Design, Synthesis, and Evaluation of Tetrasubstituted Pyridines as Potent 5-HT2C Receptor Agonists.
| S-EPMC4360148 | biostudies-literature
Unknown Novel Coumarin 7-Carboxamide/Sulfonamide Derivatives as Potential Fungicidal Agents: Design, Synthesis, and Biological Evaluation.
| S-EPMC9611003 | biostudies-literature
Unknown Design, synthesis, molecular docking studies and biological evaluation of thiazole carboxamide derivatives as COX inhibitors.
| S-EPMC9987136 | biostudies-literature
Unknown Design, synthesis and biological evaluation of sulfamethazine derivatives as potent neuraminidase inhibitors.
| S-EPMC11244698 | biostudies-literature
Unknown Design, Synthesis and Pharmacological Evaluation of Naphthofuran Derivatives as Potent SIRT1 Activators.
| S-EPMC8113817 | biostudies-literature
Unknown Design, Synthesis, and Biological Evaluation of 3-Amino-pyrazine-2-carboxamide Derivatives as Novel FGFR Inhibitors.
| S-EPMC11571013 | biostudies-literature
Unknown Synthesis and Biological Activity Evaluation of Coumarin-3-Carboxamide Derivatives.
| S-EPMC8002271 | biostudies-literature
Unknown Design, synthesis, and evaluation of potent novel peroxisome proliferator-activated receptor γ indole partial agonists.
| S-EPMC7243741 | biostudies-literature