Discovery and preclinical development of AR453588 as an anti-diabetic glucokinase activator.,Bioorganic & Medicinal Chemistry

当前位置： X-MOL 学术 › Bioorg. Med. Chem. › 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.)

Discovery and preclinical development of AR453588 as an anti-diabetic glucokinase activator.
Bioorganic & Medicinal Chemistry ( IF 3.3 ) Pub Date : 2019-12-02 , DOI: 10.1016/j.bmc.2019.115232
Ronald J Hinklin ₁ , Brian R Baer ₁ , Steven A Boyd ₁ , Mark D Chicarelli ₁ , Kevin R Condroski ₁ , Walter E DeWolf ₁ , John Fischer ₁ , Michele Frank ₁ , Gary P Hingorani ₁ , Patrice A Lee ₁ , Nickolas A Neitzel ₁ , Scott A Pratt ₁ , Ajay Singh ₁ , Francis X Sullivan ₁ , Timothy Turner ₁ , Walter C Voegtli ₁ , Eli M Wallace ₁ , Lance Williams ₁ , Thomas D Aicher ₁

Affiliation

Glucose flux through glucokinase (GK) controls insulin release from the pancreas in response to high levels of glucose. Flux through GK is also responsible for reducing hepatic glucose output. Since many individuals with type 2 diabetes appear to have an inadequacy or defect in one or both of these processes, identifying compounds that can activate GK could provide a therapeutic benefit. Herein we report the further structure activity studies of a novel series of glucokinase activators (GKA). These studies led to the identification of pyridine 72 as a potent GKA that lowered post-prandial glucose in normal C57BL/6J mice, and after 14d dosing in ob/ob mice.

中文翻译：

作为抗糖尿病葡萄糖激酶激活剂的AR453588的发现和临床前开发。

通过葡萄糖激酶（GK）的葡萄糖通量控制胰岛素响应于高水平的葡萄糖而从胰腺释放。通过GK的通量还负责降低肝脏的葡萄糖输出量。由于许多2型糖尿病患者似乎在这些过程中的一个或两个过程中均存在不足或缺陷，因此鉴定可激活GK的化合物可提供治疗益处。在本文中，我们报告了一系列新型的葡萄糖激酶激活剂（GKA）的进一步的结构活性研究。这些研究导致将吡啶72鉴定为有效的GKA，可降低正常C57BL / 6J小鼠以及在ob / ob小鼠给药14d后降低餐后葡萄糖。

更新日期：2019-12-02

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