The synthesis of new biologically active substances among 4-amino-5-alkyl-1,2,4-triazole(4H)-3-yl-thioacetanilides and their chemical modification

Abstract

The synthesis of a series of new 4-amino-5-alkyl-1,2,4-triazole(4H)-3-yl thioacetanilides and 4-pyrrolyl-5-alkyl-1,2,4-triazole(4H)-3-yl thioacetanilides has been described in the article. The key intermediates – 4-amino-5-alkyl-3-mercapto-1,2,4-triazoles(4H) 4a-c were synthesized started from the corresponding carboxylic acids (acetic, propanoic and butanoic) after their esterification followed by hydrazinolysis, CS2 reaction and cyclisation under hydrazine hydrate. The first group of substances 6a-p was obtained by alkylation of the key intermediate 4a-c with chloroacetic acid anilides in the presence of basic catalysts. The subsequent modification under conditions of Paal-Knorr reaction led to the corresponding pyrrolyl derivatives 7a-p. The structure of the compounds synthesized has been proven by the data of elemental analysis and NMR spectra. In NMR-spectra the result of alkylation has been confirmed by disappearance of the chemical shift of the mercapto group. All compounds both intermediate 4a-c and end products 6a-u and 7a-u contain signals of the alkyl protons of substituents in the triazole (methyl or methyl and methylene) ring; the 4-aminogroup protons are in the spectra of compounds 6 as singlet signals at 5.87-5.92 ppm. Modification of amino derivatives 6 into pyrrolyl substituted 7 is accompanied with the appearance of the characteristic signals of methyne protons of the pyrrole moiety instead of the signal of the amino group – triplet (positions 3,4) at 6.30-6.31 ppm and doublet (positions 2,5) at 7.21-7.24 ppm. Substances 7a, 7f, 7j and 7m were tested on the antitumour activity in vitro. As the result of this investigation it was noted that unfortunately all substances selected were not effective inhibitors of tumour cells in this dose.