title: The discovery of oxazolones-grafted spirooxindoles via three-component diversity oriented synthesis and their preliminary biological evaluation.
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.
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, 610041, PR China.
authors.forename: Hui
authors.initials: H
authors.lastname: Dong
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, 610041, PR China.
authors.forename: Sicheng
authors.initials: S
authors.lastname: Song
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, 610041, PR China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Chunyun
authors.initials: C
authors.lastname: Xu
authors.affiliation: 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.
authors.forename: Haowei
authors.initials: H
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Liang
authors.initials: L
authors.lastname: Ouyang
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001391:Azo Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001597:Benzylidene Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D061565:Cycloaddition Reaction; D055808:Drug Discovery; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D008958:Models, Molecular; D009369:Neoplasms / Q000188:drug therapy; D010081:Oxazolone / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000078183:Oxindoles; D011759:Pyrrolidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013141:Spiro Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013237:Stereoisomerism; D013882:Thiosemicarbazones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D001391:Azo Compounds; D001597:Benzylidene Compounds; D007211:Indoles; D000078183:Oxindoles; D011759:Pyrrolidines; D013141:Spiro Compounds; D013882:Thiosemicarbazones; C512188:azomethine; C022960:2-oxindole; C018361:2-phenyloxazolone; D010081:Oxazolone; C032519:pyrrolidine
keywords: 1,3-Dipolar cycloaddition; Azomethine ylides; Multi-component reactions; Spirooxindole derivatives