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

Hui Dong; Sicheng Song; Jingjing Li; Chunyun Xu; Haowei Zhang; Liang Ouyang

doi:10.1016/j.bmcl.2015.06.076

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. Epub 2015 Jun 27.

Authors

Hui Dong¹, Sicheng Song¹, Jingjing Li¹, Chunyun Xu², Haowei Zhang², Liang Ouyang³

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: [email protected].

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry*
Antineoplastic Agents / pharmacology*
Azo Compounds / chemical synthesis
Azo Compounds / chemistry
Azo Compounds / pharmacology
Benzylidene Compounds / chemical synthesis
Benzylidene Compounds / chemistry
Benzylidene Compounds / pharmacology
Cell Line, Tumor
Cycloaddition Reaction
Drug Discovery
Humans
Indoles / chemical synthesis
Indoles / chemistry*
Indoles / pharmacology*
Models, Molecular
Neoplasms / drug therapy
Oxazolone / analogs & derivatives
Oxazolone / chemical synthesis
Oxazolone / chemistry
Oxazolone / pharmacology
Oxindoles
Pyrrolidines / chemical synthesis
Pyrrolidines / chemistry
Pyrrolidines / pharmacology
Spiro Compounds / chemical synthesis
Spiro Compounds / chemistry*
Spiro Compounds / pharmacology*
Stereoisomerism
Thiosemicarbazones / chemical synthesis
Thiosemicarbazones / chemistry
Thiosemicarbazones / pharmacology

Substances

Antineoplastic Agents
Azo Compounds
Benzylidene Compounds
Indoles
Oxindoles
Pyrrolidines
Spiro Compounds
Thiosemicarbazones
azomethine
2-oxindole
2-phenyloxazolone
Oxazolone
pyrrolidine