Synthesis and the study of the antimicrobial activity of 3-amino-5-methyl-2-(alkylthio)-4-oxo-n-aryl-3,4-dihydrothieno[2,3-d]pyrimidine-6-carboxamides

Abstract

By alkylation of 3-amino-5-methyl-4-oxo-N-aryl-2-thioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidine- 6-carboxamides with substituted benzylchlorides and chloroacetic acid the series of novel derivatives of 3-amino-5-methyl-2-(alkylthio)-4-oxo-N-aryl-3,4-dihydrothieno[2,3-d]pyrimidine-6-carboxamides have been obtained. The structures of these compounds have been confirmed by ¹H NMR spectral data and the elemental analysis. For all of the products obtained the ¹H NMR spectra contain the signals of the amino group as the sharp singlet in the region of 5.75-5.84 ppm, the signal of the methyl group at position 5 of the thieno[2,3-d]pyrimidine system (2.68-2.75 ppm); the signal of the carboxamide NH group, which position varies from 9.67 ppm to 10.61 ppm depending on the structure of the substituent of the amide aromatic cycle, is also observed. In the spectra the signals of the benzyl CH₂ group protons are located in the region of 4.23-4.29 ppm, while the same signal for the derivative of thioacetic acid is observed at 3.82 ppm. The antimicrobial activity screening for the compounds obtained has been performed by the agar well diffusion method. In general, it has been found that all of the compounds tested appeared to be more active than the reference drugs against the strains of both Proteus vulgaris and Pseudomonas aeruginosa; 3-amino-2-(benzylthio)-5-methyl- N-(4-methylphenyl)-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidine-6-carboxamide was the most active compound, which moderately inhibited the growth of all test-strains of microorganisms, and showed even higher activity than the reference drugs streptomycin and metronidazole against Bacillus subtilis and Candida albicans fungi.