Registration Number
0219U102055,
0119U102553
, R & D reports
Title
The evaluation of biological activity and mechanism of action among novel thiazolidinone derivatives as promissing antimicrobial agents
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Head
Lesyk Roman B., Доктор фармацевтичних наук
Registration Date
16-12-2019
Organization
Danylo Halytsky Lviv National Medical University
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Synthesis of drug-like molecules was performed by conjugation of 4-thiazolidinone or thiazole moieties with known "biophore" heterocyclic systems, in particular the pyridine and thiopyran, which allows to preserve the pharmacological profile of these compounds and to analyze the structure-activity relationship. On the basis of logic-structural approach, the optimal directions of synthesis and structural modification of the target compounds were performed under reactions of [3+3]/[4 + 2]-cyclocondensation, N-alkylation, aminolysis and acylation. The sub-library of 5-arylidene and 5-aminomethylene-4-thiazolidinones, thiazolo[4,5-b]pyridines and thiopyrano[2,3-d]thiazoles was designed and synthesized . The synthesis of biologically active 5-R,R'-aminomethylene derivatives of thiazolidine-2,4-dione and 4-thioxothiazolidin-2-one and rel-(5R,6S,7S)-6-benzoyl-2-oxo-7-aryl-3,5,6,7-tetrahydro-2H-thiopyran[2,3-d]thiazole-5-carboxylic acids was accomplished. Thiazolidin-2,4-dione and 4-thioxothiazolidin-2-one have been shown to be effective reagents in reactions with triethylorthoformate in the acetanhydride medium for further interaction with amines as nucleophiles providing to various of 5-R,R'-aminomethylene thiazolidinones. The using of the [4+2]-cyclocondensation reaction of 5-arylidene-isorodanines with beta-aroylacrylic acids is an effective regio- and diastereoselective method for the synthesis of novel thiopyrano[2,3-d]thiazole-5-carboxylic acids. On the basis of complex NMR analysis and X-ray analysis the structure of 2-(5-aminomethylene-4-oxo-2-thioxothiazolidin-3-yl)-3-phenylpropionic acid derivatives was determined. Conducted screening studies of the pharmacological activity of the synthesized compounds allowed to identify a number of promising agents with antimicrobial activity, as well as to establish some patterns of correlation "structure-activity" relationship.
Product Description
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Kaminskyy Danylo V.
Kryshchyshyn Anna P.
Lesyk Roman B.
Lozynskyi Andrii V.
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2020-04-02
