Design, synthesis and biological evaluation of novel pyrimidinedione derivatives as DPP-4 inhibitors

被引：30

作者：

Li, Ning ^{[1
,2
,3
,4
]}

Wang, Li-Jun ^{[1
,2
,4
]}

Jiang, Bo ^{[1
,2
,4
]}

Guo, Shu-Ju ^{[1
,2
,4
]}

Li, Xiang-Qian ^{[1
,2
,4
]}

Chen, Xue-Chun ^{[5
]}

Luo, Jiao ^{[1
,2
,3
,4
]}

Li, Chao ^{[1
,2
,3
,4
]}

Wang, Yi ^{[5
]}

Shi, Da-Yong ^{[1
,2
,3
,4
]}

机构：

[1] Chinese Acad Sci, Inst Oceanol, Key Lab Expt Marine Biol, Qingdao 266071, Peoples R China

[2] Qingdao Natl Lab Marine Sci & Technol, Lab Marine Drugs & Bioprod, Qingdao 266235, Peoples R China

[3] Univ Chinese Acad Sci, Beijing 100049, Peoples R China

[4] Chinese Acad Sci, Ctr Ocean Mega Sci, Qingdao 266071, Peoples R China

[5] Zhejiang Univ, Coll Pharmaceut Sci, Hangzhou 310058, Zhejiang, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2018年 / 28卷 / 12期

基金：

美国国家科学基金会; 中国国家自然科学基金;

关键词：

Pyrimidinedionederivatives; DPP-4; inhibitor; Molecular hybrid; SARs; Type; 2; diabetes; ALGA RHODOMELA-CONFERVOIDES; DIPEPTIDYL PEPTIDASE-4 INHIBITORS; PHOSPHATASE 1B INHIBITOR; C57BL/KSJ-DB/DB MICE; BROMOPHENOLS; DISCOVERY; HPN;

D O I：

10.1016/j.bmcl.2018.05.022

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of novel pyrimidinedione derivatives were designed and evaluated for in vitro dipeptidyl peptidase-4 (DPP-4) inhibitory activity and in vivo anti-hyperglycemic efficacy. Among them, the representative compounds 11, 15 and 16 showed excellent inhibitory activity of DPP-4 with IC50 values of 64.47 nM, 188.7 nM and 65.36 nM, respectively. Further studies revealed that compound 11 was potent in vivo hypoglycemic effect. The structure-activity relationships of these pyrimidinedione derivatives had been discussed, which would be useful for developing novel DPP-4 inhibitors as treating type 2 diabetes.

引用

页码：2131 / 2135

页数：5

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