SYNTHESIS AND CONVERSION OF NEW POTENTIALLY BIOLOGICALLY ACTIVE 4-THIAZOLIDINONE DERIVATIVES WITH A TRIAZINOINDOLE FRAGMENT IN THE MOLECULES

Abstract

A wide spectrum of biological activity and the possibility of diverse chemical modification of isatinderivatives prompts the search for new highly active compounds as potential drugs among condensed and noncondensedheterocyclic systems containing the specified molecular "matrix". Studies of 1,2,4-triazino[5,6-b]indoles,the chemical precursors of which are isatins, have shown the prospect of their use in the treatment of oncologicaldiseases. In addition, potential antifungal, antiviral, antihypertensive agents have been identified among thesederivatives.Adhering to the main synthetic strategy of our research, which is based on the "hybrid-pharmacophoric" approach inthe synthesis of new heterocyclic derivatives of 4-thiazolidinone, in our opinion, the combination of the mainscaffold (4-thiazolidinone) and the structural "imitator" is interesting and promising of the isatin "matrix" -triazinoindole fragment, as well as the synthesis of new polyheterocyclic ensembles, including those with apharmacologically attractive pyrazoline fragment. Under the conditions of the S-alkylation reaction of 3-mercapto-5H-1,2,4-triazino[5,6-b]indoles, 2-chloro-1-(3,5-diaryl-4,5-dihydropyrazole- 1-yl)ethanones, which made it possibleto obtain 1,2,4-triazino[5,6-b]indole-pyrazolines with preparative yields. By hydrazinolysis of 3-mercapto-5H-1,2,4-triazino[5,6-b]indoles, corresponding hydrazines were obtained, which were successfully used for the first time inthe Holmberg reaction, and derivatives of the triazinoindole-thiazolidinone system were obtained – 3-(1,2 ,4-triazino[5,6-b]indol-3-ylamino-2-thioxothiazolidin-4-ones Chemical modification of methylene-active compoundswas carried out under the conditions of the Kniovenagel reaction with aromatic aldehydes and isatin derivatives,which was substantiated by the results of biological studies of structurally related heteryl-substituted 5-ylidenerhodanines. The synthesis of derivatives of the 4-thiazolidinone-thiadiazinoindole system, which is based onthe interaction of N-(1,3,4-thiadiazinoindol-2-yl)-2-chloroacetamides with ammonium thiocyanate in an acetonemedium, was carried out. The obtained conjugates are methylene-active compounds, which made it possible tosynthesize a series of 5-arylidene derivatives under the conditions of the Kniovenagel reaction. The purpose of thework is to experimentally confirm or refute the feasibility of chemical modification of isatin into the triazineindolinesystem and its combination with 4-thiazolidinone biophore for the search of new biologically activecompounds, including highly active antitumor agents. The structure of the synthesized compounds was confirmedby NMR spectroscopy. To study the structure in the solid state, the IR spectra of the key compounds in KBr tabletswere studied.