Discovery of novel selective GPR120 agonists with potent anti-diabetic activity by hybrid design

被引：13
作者：
Sheng, Ren [1 ,2 ]
Yang, Liu [3 ,4 ]
Zhang, Yanchun [1 ,2 ]
Xing, Enming [1 ,2 ]
Shi, Rui [1 ,2 ]
Wen, Xiaoan [1 ,2 ]
Wang, Heyao [3 ]
Sun, Hongbin [1 ,2 ]
机构：
[1] China Pharmaceut Univ, Jiangsu Key Lab Drug Discovery Metab Dis, 24 Tongjia Xiang, Nanjing 210009, Jiangsu, Peoples R China
[2] China Pharmaceut Univ, State Key Lab Nat Med, 24 Tongjia Xiang, Nanjing 210009, Jiangsu, Peoples R China
[3] Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China
[4] Univ Chinese Acad Sci, Beijing 100049, Peoples R China
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2018年 / 28卷 / 15期
基金：
中国国家自然科学基金;
关键词：
GPR120; Agonist biphenyl derivatives; OGTT; Type; 2; diabetes; RECEPTOR; 4; FFA4/GPR120; IDENTIFICATION; SECRETION;
D O I：
10.1016/j.bmcl.2018.06.047
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
GPR120 is an attractive target for the treatment of type 2 diabetes. In this study, a series of biphenyl derivatives were designed, synthesized by hybrid design. The selected compound 6a exhibited potent GPR120 agonist activity (EC50 = 93 nM) and high selectivity over GPR40. The results of oral glucose tolerance test (OGTT) demonstrated that 6a exhibited significant glucose-lowering effect in glucose-loaded ICR male mice. Analysis of the structure-activity relationship is also presented. Compound 6a deserves further biological evaluation and structural modifications.
引用
收藏
页码：2599 / 2604
页数：6
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