Synthesis and anti-diabetic activity of novel biphenylsulfonamides as glucagon receptor antagonists,Chemical Biology & Drug Design

当前位置： X-MOL 学术 › Chem. Bio. Drug Des. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Synthesis and anti-diabetic activity of novel biphenylsulfonamides as glucagon receptor antagonists
Chemical Biology & Drug Design ( IF 3.2 ) Pub Date : 2021-07-26 , DOI: 10.1111/cbdd.13928
Chang-Yong Lee ₁ , Hojung Choi _{1,

2} , Eun-Young Park ₃ , Thi-Thao-Linh Nguyen ₁ , Han-Joo Maeng ₁ , Kyoung Mee Lee ₄ , Hee-Sook Jun _{1,

2,

5} , Dongyun Shin ₁

Affiliation

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.

中文翻译：

新型联苯磺酰胺胰高血糖素受体拮抗剂的合成及其抗糖尿病活性

2型糖尿病的特点是慢性高血糖。胰岛素是一种由胰腺 β 细胞分泌的激素，可降低血糖水平；而胰高血糖素是一种由胰腺 α 细胞分泌的激素，可通过刺激肝葡萄糖产生来反调节胰岛素，从而升高血糖水平。在糖尿病患者中，胰高血糖素分泌失调会导致高血糖。因此，抑制胰高血糖素受体是治疗2型糖尿病高血糖的一种策略。在本文中，我们报道了一系列联苯磺酰胺衍生物，这些衍生物经过设计、合成，然后通过 cAMP 和肝葡萄糖生成测定法进行评估，作为胰高血糖素受体拮抗剂。其中，在体外测定中，化合物7aB-3减少胰高血糖素诱导的cAMP产生和胰高血糖素诱导的葡萄糖产生。胰高血糖素激发试验和葡萄糖耐量试验表明，化合物7aB-3显着抑制胰高血糖素诱导的血糖升高并改善葡萄糖耐量。这些结果表明化合物7aB-3具有治疗2型糖尿病的治疗潜力。

更新日期：2021-07-26

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文本刊介绍/投稿指南11