Synthesis and the antimicrobial activity of 5-methyl-6-(2-methyl-1,3-thiazol-4-yl)-3-phenylthieno[2,3-d]pyrimidine-2,4(1H,3H)-diones

S. V. Vlasov, T. P. Osolodchenko, S. M. Kovalenko, V. P. Chernykh

Abstract


By the reaction of 3-phenyl-6-(α-bromoacetyl)-5-methylthieno[2,3-d]pyrimidine-2,4(1H,3H)-dione with thioacetamide 5-methyl-6-(2-methyl-1,3-thiazol-4-yl)-3-phenylthieno[2,3-d]pyrimidine-2,4(1H,3H)-dione was obtained; further the compound was modified by alkylation of its position 1 with benzyl chlorides and chloroacetamides. The structures of the compounds obtained have been confirmed by 1H NMR and mass-spectral data. All the 1H NMR spectra of the compounds obtained have the signals of thiazole cycle at 7.62-7.57 ppm, for 1-alkyl-5-methyl-6-(2-methyl-1,3-thiazol-4-yl)-3-phenylthieno[2,3-d] pyrimidine-2,4(1H,3H)-diones the signals of the methylene group protons are observed in the range of 5.13-5.21 ppm for benzyl substituted derivatives and 4.78-4.82 ppm for the compounds with the acetamide fragment; the last ones also contain the sharp signal of NH proton in the range of 9.68- 10.41 ppm. 5-Methyl-6-(2-methyl-1,3-thiazol-4-yl)-3-phenylthieno[2,3-d]pyrimidine-2,4(1H,3H)-dione showed the antimicrobial activity against Staphylococcus aureus higher than the reference drugs Metronidazole and Streptomycin, it also appeared to be moderately active against Pseudomonas aeruginosa and Candida albicans fungi. The antimicrobial activity of 1-alkyl-5-methyl-6-(2-methyl- 1,3-thiazol-4-yl)-3-phenylthieno[2,3-d]pyrimidine-2,4(1H,3H)-diones is inferior to the activity of the compound with the hydrogen atom in position 1; the highest activity has been determined for the derivative with 4-methylbenzyl substituent in position 1, which inhibits the growth of Staphylococcus aureus and Candida albicans.


Keywords


thiophene; pyrimidine; alkylation; thiazole

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References


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DOI: https://doi.org/10.24959/88973

Abbreviated key title: Vìsn. farm.

ISSN 2415-8844 (Online), ISSN 1562-7241 (Print)