Discovery of dipeptidyl peptidase IV (DPP4) inhibitors based on a novel indole scaffold

被引：11
作者：
Xiao, Peng-Fei [1 ,2 ]
Guo, Rui [3 ]
Huang, Shao-Qiang [2 ]
Cui, Heng-Jun [3 ]
Ye, Sheng [3 ]
Zhang, Zhiyuan [2 ]
机构：
[1] Peking Union Med Coll, Beijing 100730, Peoples R China
[2] Natl Inst Biol Sci, Beijing 102206, Peoples R China
[3] Zhejiang Univ, Inst Life Sci, Hangzhou 310058, Zhejiang, Peoples R China
来源：
CHINESE CHEMICAL LETTERS | 2014年 / 25卷 / 05期
关键词：
DPP4; inhibitor; Type; 2; diabetes; De nova design; Indole scaffold; Crystal structure; STRUCTURE-BASED DESIGN; HIGHLY POTENT; SITAGLIPTIN; SAXAGLIPTIN;
D O I：
10.1016/j.cclet.2014.03.047
中图分类号：
O6 [化学];
学科分类号：
0703 ;
摘要：
Dipeptidyl peptidase IV (DPP4) inhibitors are proven in the treatment of type 2 diabetes. We designed and synthesized a series of novel indole compounds that selectively inhibit the activity of DPP4 over dipeptidyl peptidase 9 (DPP9) (>200 fold). We further co-crystallized DPP4 with indole sulfonamide (compound 1) to confirm a proposed binding mode. Good metabolic stability of the indole compounds represents another positive attribute for further development. (C) 2014 Sheng Ye and Zhiyuan Zhang. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
引用
收藏
页码：673 / 676
页数：4
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