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

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 compoun...

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Autores principales: Zhao, Shizhen, Wang, Le, Wang, Jie, Wang, Chenwei, Zheng, Shaowei, Fu, Yajie, Li, Yunfu, Chen, Wei-Dong, Hou, Ruifang, Yang, Dongbin, Wang, Yan-Dong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society of Chemistry 2022
Materias:
Chemistry
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8979340/
https://www.ncbi.nlm.nih.gov/pubmed/35425398
http://dx.doi.org/10.1039/d1ra08867j
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author Zhao, Shizhen
Wang, Le
Wang, Jie
Wang, Chenwei
Zheng, Shaowei
Fu, Yajie
Li, Yunfu
Chen, Wei-Dong
Hou, Ruifang
Yang, Dongbin
Wang, Yan-Dong
author_facet Zhao, Shizhen
Wang, Le
Wang, Jie
Wang, Chenwei
Zheng, Shaowei
Fu, Yajie
Li, Yunfu
Chen, Wei-Dong
Hou, Ruifang
Yang, Dongbin
Wang, Yan-Dong
author_sort Zhao, Shizhen
collection PubMed
description 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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spelling pubmed-89793402022-04-13 Design, synthesis and evaluation of 3-phenoxypyrazine-2-carboxamide derivatives as potent TGR5 agonists Zhao, Shizhen Wang, Le Wang, Jie Wang, Chenwei Zheng, Shaowei Fu, Yajie Li, Yunfu Chen, Wei-Dong Hou, Ruifang Yang, Dongbin Wang, Yan-Dong RSC Adv Chemistry 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. The Royal Society of Chemistry 2022-01-27 /pmc/articles/PMC8979340/ /pubmed/35425398 http://dx.doi.org/10.1039/d1ra08867j Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by-nc/3.0/
spellingShingle Chemistry
Zhao, Shizhen
Wang, Le
Wang, Jie
Wang, Chenwei
Zheng, Shaowei
Fu, Yajie
Li, Yunfu
Chen, Wei-Dong
Hou, Ruifang
Yang, Dongbin
Wang, Yan-Dong
Design, synthesis and evaluation of 3-phenoxypyrazine-2-carboxamide derivatives as potent TGR5 agonists
title Design, synthesis and evaluation of 3-phenoxypyrazine-2-carboxamide derivatives as potent TGR5 agonists
title_full Design, synthesis and evaluation of 3-phenoxypyrazine-2-carboxamide derivatives as potent TGR5 agonists
title_fullStr Design, synthesis and evaluation of 3-phenoxypyrazine-2-carboxamide derivatives as potent TGR5 agonists
title_full_unstemmed Design, synthesis and evaluation of 3-phenoxypyrazine-2-carboxamide derivatives as potent TGR5 agonists
title_short Design, synthesis and evaluation of 3-phenoxypyrazine-2-carboxamide derivatives as potent TGR5 agonists
title_sort design, synthesis and evaluation of 3-phenoxypyrazine-2-carboxamide derivatives as potent tgr5 agonists
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8979340/
https://www.ncbi.nlm.nih.gov/pubmed/35425398
http://dx.doi.org/10.1039/d1ra08867j
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