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Synthesis and anti‐diabetic activity of novel biphenylsulfonamides as glucagon receptor antagonists
Author(s) -
Lee ChangYong,
Choi Hojung,
Park EunYoung,
Nguyen ThiThaoLinh,
Maeng HanJoo,
Mee Lee Kyoung,
Jun HeeSook,
Shin Dongyun
Publication year - 2021
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.13928
Subject(s) - glucagon , medicine , endocrinology , glucagon receptor , insulin , hormone , stimulation , type 2 diabetes , receptor , diabetes mellitus , in vitro , chemistry , biochemistry
Type 2 diabetes is characterized by chronic hyperglycemia. Insulin, a hormone secreted from pancreatic β‐cells, decreases blood glucose levels, and glucagon, a hormone secreted from pancreatic α‐cells, increases blood glucose levels by counterregulation of insulin through stimulation of hepatic glucose production. In diabetic patients, dysregulation of glucagon secretion contributes to hyperglycemia. Thus, inhibition of the glucagon receptor is one strategy for the treatment of hyperglycemia in type 2 diabetes. In this paper, we report a series of biphenylsulfonamide derivatives that were designed, synthesized, and then evaluated by cAMP and hepatic glucose production assays as glucagon receptor antagonists. Of these, compound 7aB‐3 decreased glucagon‐induced cAMP production and glucagon‐induced glucose production in the in vitro assays. Glucagon challenge tests and glucose tolerance tests showed that compound 7aB‐3 significantly inhibited glucagon‐induced glucose increases and improved glucose tolerance. These results suggest that compound 7aB‐3 has therapeutic potential for the treatment of type 2 diabetes.