SYNTHESIS AND CONVERSION OF NEW POTENTIALLY BIOLOGICALLY ACTIVE 4-THIAZOLIDINONE DERIVATIVES WITH A TRIAZINOINDOLE FRAGMENT IN THE MOLECULES
DOI:
https://doi.org/10.35120/kij5404677hKeywords:
isatin, synthesis, 4-thiazolidinoneAbstract
A wide spectrum of biological activity and the possibility of diverse chemical modification of isatin
derivatives prompts the search for new highly active compounds as potential drugs among condensed and noncondensed
heterocyclic 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 oncological
diseases. In addition, potential antifungal, antiviral, antihypertensive agents have been identified among these
derivatives.
Adhering to the main synthetic strategy of our research, which is based on the "hybrid-pharmacophoric" approach in
the synthesis of new heterocyclic derivatives of 4-thiazolidinone, in our opinion, the combination of the main
scaffold (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 a
pharmacologically 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 possible
to 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 in
the 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 compounds
was 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 on
the interaction of N-(1,3,4-thiadiazinoindol-2-yl)-2-chloroacetamides with ammonium thiocyanate in an acetone
medium, was carried out. The obtained conjugates are methylene-active compounds, which made it possible to
synthesize a series of 5-arylidene derivatives under the conditions of the Kniovenagel reaction. The purpose of the
work is to experimentally confirm or refute the feasibility of chemical modification of isatin into the triazineindoline
system and its combination with 4-thiazolidinone biophore for the search of new biologically active
compounds, including highly active antitumor agents. The structure of the synthesized compounds was confirmed
by NMR spectroscopy. To study the structure in the solid state, the IR spectra of the key compounds in KBr tablets
were studied.
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