Synthesis of new pyrazoline-thiazoles and their biological activity

D. Ya. Havrylyuk


The application of the [2+3]-cyclocondensation reaction for the synthesis of 2-pyrazoline substituted thiazolidinones, as well as bioisosteric pyrazoline-thiazoles has been analyzed. Following the literature data 4,5-dihydro- 1-carbothioamides are used as S,N-binucleophiles in the [2+3]-cyclocondensation reaction with different equivalents of the dielectrophilic synthon [C2]2+ (α-halogencarboxylic acids, derivatives of maleic acid, aroylacrylic acids, dimethyl ester of acetylenedicarboxylic acid, α-bromoacetophenones and ethyl 4-chloroacetoacetate). It has allowed to identify the highly active compounds with the antimicrobial, antiviral, anti-inflammatory, antitumor and antiparasitic activities. Aiming to enlarge a scope of 3,5-diaryl-4,5-dyhidropyrazol-1-carbothioamides as S,N-binucleophiles in [2+3]-cyclization and to find a new chemotherapeutic agents the synthesis of new pyrazoline-thiazoles has been carried out; it is based on the reaction between the carbothioamides mentioned and ethyl 2-chloroacetoacetate or 3-chloroacetyl acetone in the presence of fused sodium acetate in refluxing acetic acid. The structure of the compounds synthesized has been confirmed by 1H NMR spectra. The screening of the antitumor and antitrypanosomal activities of some compounds synthesized has been conducted. As a result of in vitro experiments their moderate cytotoxicity in the concentration of 10-5 mol/l for individual cancer cell lines has been identified. At the same time a high trypanocidal activity of compounds 2h and 2j has been determined against Trypanosoma brucei gambiense strain with the values of ІC50 of 3.82 and 2.61μM, respectively; and it exceeds the activity of the reference medicine nifurtomox.


synthesis; thiazoles; pyrazolines; [2+3]-cyclization; biological activity


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Abbreviated key title: J. Org. Pharm. Chem.

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