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

Bioorg Med Chem Lett. 2015 Sep 1;25(17):3585-91. doi: 10.1016/j.bmcl.2015.06.076.

Hui Dong ¹, Sicheng Song ¹, Jingjing Li ¹, Chunyun Xu ², Haowei Zhang ², Liang Ouyang ³

Affiliations

1 State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, 610041, PR China.
2 State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, 610041, PR China; West China School of Pharmacy, Sichuan University, 610041, PR China.
3 State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, 610041, PR China. Electronic address: ouyangliang@scu.edu.cn.

PMID: 26159483 DOI: 10.1016/j.bmcl.2015.06.076

Abstract

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.

Keywords

1,3-Dipolar cycloaddition; Azomethine ylides; Multi-component reactions; Spirooxindole derivatives.

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