Design, Synthesis and Biological Evaluation of Novel Imidazolone Derivatives as Dipeptidyl Peptidase 4 Inhibitors

被引：1

作者：

Liu, Yang ^{[1
]}

Jiang, Chaoyi ^{[1
]}

Wu, Haoshu ^{[2
]}

Wu, Peng ^{[1
]}

Si, Meimei ^{[2
]}

Hu, Yongzhou ^{[1
]}

Liu, Tao ^{[1
]}

机构：

[1] Zhejiang Univ, Coll Pharmaceut Sci, ENS Joint Lab Med Chem, Hangzhou 310058, Zhejiang, Peoples R China

[2] Zhejiang Univ, Coll Pharmaceut Sci, Inst Pharmacol & Toxicol, Hangzhou 310058, Zhejiang, Peoples R China

来源：

MEDICINAL CHEMISTRY | 2013年 / 9卷 / 07期

关键词：

Diabetes; docking; DPP-4; inhibitors; drug design; imidazolone; synthesis; IV INHIBITORS; MEDICINAL CHEMISTRY; POTENT;

D O I：

10.2174/1573406411309070007

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of novel imidazolone derivatives were designed and synthesized via a rational drug design strategy. These compounds were obtained from 3-substituted imidazolidine-2,4-dione through alkylation, formylation, dehydration, and amination. The structures were characterized by H-1 NMR, C-13 NMR, and MS. All target compounds were screened for their DPP-4 inhibitory activity in vitro. The results revealed that some imidazolone derivatives showed potent DPP-4 inhibition. Compound 5b had an IC50 value of 2.21 mu M inhibitory activity against DPP-4. As a promising lead compound, compound 5b with DPP-4 binding mode was further studied by docking analysis. The expected interaction mode was obtained.

引用

页码：938 / 946

页数：9

共 16 条

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