The chemistry of isothiazoles is being intensively developed, which is evidenced by the wide range of selective transformations involving the isothiazole heterocycle and the high biological activity of its derivatives that can be used as effective new drugs and plant protection chemicals. Some representatives of isothiazoles have proven to be synergists of bioactive substances, which opens the way to lower the doses of drugs used and is especially important in cancer chemotherapy. In the framework of the present review, the accomplishments in the chemistry of isothiazoles over the past 18 years are examined, whilst current strategies for the synthesis of isothiazole-containing molecules and key directions of studies in this field of heterocyclic chemistry are discussed. Considerable attention is paid to chlorinated isothiazoles and strategies for their use in the synthesis of biologically active substances. In addition, a comprehensive review of existing literature in the field of metal complexes of isothiazoles is given, including the results and prospects for the practical use of isothiazole–metal complexes as catalysts for cross-coupling reactions in aqueous and aqueous–alcoholic media (‘green chemistry’).1 Introduction2 Synthesis by Ring-Forming Reactions2.1 Intramolecular Cyclization2.2 (4+1)-Heterocyclization2.3 (3+2)-Heterocyclization2.4 Syntheses by Ring Transformations3 Isothiazoles by Ring Functionalization Reactions: Nucleophilic Substitution, Cross-Coupling and Side-Chain Functionalization4 Selected Syntheses of Biologically Active Isothiazole Derivatives5 Isothiazoles in the Synthesis of Transition-Metal Complexes and in Metal-Complex Catalysis6 Conclusion

Neuroepithelial tumor cells were cultured in vitro. The biopsy material was taken from 93 children at removal of the brain tumors during neurosurgical operations. The individual features of the cells sensitivity of primary cultures in respect to protocol-approved chemotherapy drugs and changes in the Interleukin-6 (Il-6) level in the culture medium after the application of chemotherapy were established. The initial level of Il-6 exceeded 600.0 pg/ml in the cultural medium with histologically verified pilomyxoid astrocytoma cells, and ranged from 100.0 to 200.0 pg/ml in the medium at cultivation of ganglioneuroblastoma and pilocytic astrocytoma. A decrease in the Il-6 level in the medium culture of primary tumors cells was observed after the application of chemotherapeutic agents on the cells of pilomyxoid astrocytoma, astrocytomas, and pilocytic desmoplastic/nodular medulloblastoma. The production of Il-6 increased after application of cytostatic drugs on the cells of oligoastrocytomas. A decrease in Il-6 level after application of Cisplatin and Methotrexate and a 5-10 fold increase in the level of Il-6 after application of Etoposide, Carboplatin, Cytarabine, and Gemcitabine were registered in the medium with ganglioneuroblastoma. To improve the cytotoxic action of chemotherapeutic agents, the combined application of cytostatics with heterocyclic compounds was carried out. A computer modeling of ligand-protein complexes of carbamide using the Dock 6.4 and USF Chimera program packages was performed with molecular mechanics method. Special attention was drawn to the ability of several isoxazole heterocycles and isothiazolyl to inhibit the tyrosine kinase. It was proved in vitro that the joint application of chemotherapeutic agents and heterocyclic compounds could reduce the concentration of the cytostatic factor by 10 or more times, having maintained the maximum cytotoxic effect. It was assumed that the target amplification of cytotoxic action of chemotherapeutic agents had prospects for reducing toxic side effects of chemotherapy in vivo, which would be carried out only after the preclinical studies.

Acylation of benzene and toluene with 5-phenyl- and 5-( p-tolyl)isoxazole-3-carbonyl chlorides gave 5-phenyl(or p-tolyl)isoxazol-3-yl phenyl(or p-tolyl)ketones which were reduced to the corresponding...

Functionally substituted 5-( p-tolyl)isoxazoles and 4,5-dichloroisothiazoles, whose molecules contain azomethine, amino, carboxyl, and ester moieties in various combinations in the aromatic ring in...