The discovery of oxazolones-grafted spirooxindoles via three-component diversity oriented synthesis and their preliminary biological evaluation

被引：40

作者：

Dong, Hui ^{[1
,2
,3
]}

Song, Sicheng ^{[1
,2
,3
]}

Li, Jingjing ^{[1
,2
,3
]}

Xu, Chunyun ^{[1
,2
,3
,4
]}

Zhang, Haowei ^{[1
,2
,3
,4
]}

Ouyang, Liang ^{[1
,2
,3
]}

机构：

[1] Sichuan Univ, West China Hosp, State Key Lab Biotherapy, Chengdu 610041, Peoples R China

[2] Sichuan Univ, West China Hosp, Ctr Canc, Chengdu 610041, Peoples R China

[3] Collaborat Innovat Ctr Biotherapy, Chengdu 610041, Peoples R China

[4] Sichuan Univ, West China Sch Pharm, Chengdu 610041, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2015年 / 25卷 / 17期

基金：

中国博士后科学基金; 中国国家自然科学基金;

关键词：

1,3-Dipolar cycloaddition; Azomethine ylides; Multi-component reactions; Spirooxindole derivatives; NATURAL-PRODUCTS; MULTICOMPONENT REACTIONS; CYCLOADDITIONS; 1,3-DIPOLAR; CHEMISTRY; PYRROLIZIDINES; STEREOCENTERS; HETEROCYCLES; DERIVATIVES; ISATIN;

D O I：

10.1016/j.bmcl.2015.06.076

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A facile method via 1,3-dipolar cycloaddition of substituted benzylidene-2-phenyloxazolone under mild conditions with azomethine ylides, which were generated in situ by a decarboxylative route from a common set of diverse isatins and amino acid derivatives was developed for a 15-membered library of regio- and stereoselective oxazolones-grafted spirooxindole-pyrrolidine, pyrrolizidines and pyrrolothiazoles. After screening their cytotoxic activities against a spectrum of cell-lines, compound 4h was identified as potent antitumor agent and inducing apoptosis. The present study has provided an effective entry to rapidly construct a chemical library of oxazolones-grafted spirooxindoles and developed a good lead compound for subsequent optimization. (C) 2015 Elsevier Ltd. All rights reserved.

引用

页码：3585 / 3591

页数：7

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