title: Synthesis and antitumor activity of substituted 3-(5-imidazo[2,1-b]thiazolylmethylene)-2-indolinones.
abstract: The synthesis of 3-(5-imidazo]2,1-blthiazolylmethylene)-2-indolinones, analogs of compounds recently published, is described. The EIZ isomerism was studied by means of nuclear Overhauser effect experiments and X-ray crystallography. All the compounds were tested as potential antitumor agents. They were also tested as potential inhibitors of cyclin-dependent kinase 1 (CDK1), in order to determine if the antitumor activity was related to this mechanism of action. The results showed that under certain substitution conditions (5-methoxy group for the indole benzene ring and 2-methyl group for the imidazothiazole system), an interesting antitumor activity was found for some compounds. From the analysis of the antitumor data, 3-1(2,6-dimethylimidazo[2,1-bJ-thiazol-5-yl)methylenel-5-methoxy-2-indolinone was the most active of the whole series.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università di Bologna, Italy. aldoandr@alma.unibo.it
authors.forename: A
authors.initials: A
authors.lastname: Andreani
authors.forename: M
authors.initials: M
authors.lastname: Granaiola
authors.forename: A
authors.initials: A
authors.lastname: Leoni
authors.forename: A
authors.initials: A
authors.lastname: Locatelli
authors.forename: R
authors.initials: R
authors.lastname: Morigi
authors.forename: M
authors.initials: M
authors.lastname: Rambaldi
authors.forename: G
authors.initials: G
authors.lastname: Giorgi
authors.forename: L
authors.initials: L
authors.lastname: Salvini
authors.forename: V
authors.initials: V
authors.lastname: Garaliene
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D016203:CDC2 Protein Kinase / Q000037:antagonists & inhibitors; D018360:Crystallography, X-Ray; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D007211:Indoles; D013844:Thiazoles; D016203:CDC2 Protein Kinase