Design and synthesis of 2-N-substituted indazolone derivatives as non-carboxylic acid glycogen synthase activators

被引：31

作者：

Qian, Yimin ^{[1
]}

Bolin, David ^{[1
]}

Conde-Knape, Karin ^{[2
]}

Gillespie, Paul ^{[1
]}

Hayden, Stuart ^{[1
]}

Huang, Kuo-Sen ^{[3
]}

Olivier, Andree R. ^{[2
]}

Sato, Tsutomu ^{[1
]}

Xiang, Qing ^{[3
]}

Yun, Weiya ^{[1
]}

Zhang, Xiaolei ^{[3
]}

机构：

[1] Hoffmann La Roche Inc, Discovery Chem, Small Mol Res, Pharmaceut Res & Early Drug Dev, Nutley, NJ 07110 USA

[2] Hoffmann La Roche Inc, Metab & Vasc Dis, Pharmaceut Res & Early Drug Dev, Nutley, NJ 07110 USA

[3] Hoffmann La Roche Inc, Discovery Technol, Small Mol Res, Pharmaceut Res & Early Drug Dev, Nutley, NJ 07110 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2013年 / 23卷 / 10期

关键词：

Glycogen synthase; Enzyme activation; Type 2 diabetes (T2D); Metabolic stability; Indazolone; N-arylation and cyclization; DEPENDENT DIABETES-MELLITUS; COUPLING REACTIONS; ARYL HYDRAZIDES; INSULIN; BROMIDES;

D O I：

10.1016/j.bmcl.2013.03.049

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Glycogen synthase (GS) catalyzes the transfer of glucose residues from UDP-glucose to a glycogen polymer chain, a critical step for glucose storage. Patients with type 2 diabetes normally exhibit low glycogen levels and decreased muscle glucose uptake is the major defect in whole body glucose disposal. Therefore, activating GS may provide a potential approach for the treatment of type 2 diabetes. In order to identify non-carboxylic acids GS activators, we designed and synthesized a series of 2-N-alkyl- and 2-N-aryl-indazolone derivatives and studied their activity in activating human GS. (C) 2013 Elsevier Ltd. All rights reserved.

引用

页码：2936 / 2940

页数：5

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