Synthesis and the antimicrobial activity 1-n-alkylated derivatives of 3-n-substituted 1H-thieno[3,2-d]pirimidine-2,4-diones

O. V. Tkachenko, S. V. Vlasov, S. M. Kovalenko, I. O. Zhuravel’, V. P. Chernykh


Two approaches for synthesis of a great variety of 3-N-substituted 1H-thieno[3,2-d]pyrimidine-2,4-diones have been investigated. The first one is based on the interaction of methyl 3-aminothiophene-2-carboxylate with isocyanates, which is a good way for preparation of 3-N-aryl-1H-thieno[3,2-d]pyrimidine-2,4-diones. The key step of the other one, which allows introduction of different alkyl substituents in position 3, is oxidation of 4-oxo-2-thioxo-2,3- dihydrothieno[3,2-d]pyrimidines prepared by interaction of 3-isothiocyanatothiophene-2-carboxylate and the primary aliphatic amines with hydrogen peroxide. Alkylation of the intermediates obtained in both ways resulted in 1-N-alkyl-3-N-substituted 1Н-thieno[3,2-d]pyrimidine-2,4-diones. 1H NMR spectra of the target molecules contain the signals of thiophene cycle protons H-6 (δ 8.02-8.18 ppm) and H-7 (δ 7.06-7.15 ppm) together with the signal of CH2 groups in position 1 of the heterocyclic system in the range of δ 4.70-5.20 ppm. The antimicrobial activity of the compounds synthesized has been investigated by the agar well diffusion method. It has been determined that the compound with phenyl substituents in position 3 and o-methylbenzyl substituent in position 1 is the most active antimicrobial agent. The 1-N-alkyl derivatives of 2,4-dioxo-1,4-dihydro-2H-thieno[3,2-d]pyrimidine-3-yl)propanoic acid benzyl amide appeared to be active against the strains of Staphylococcus aureus and Bacillus subtilis.


thiophene; pyrimidine; aromatic compounds; amides; antimicrobial substances

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Пат. WO2005049613 (2005). – Заявл.: 11.12.2004. Опубл.: 06.02.2005.

Mitsuo S., Toshiaki S., Keiichi T. et al. // Chem. Pharm. Bull. – 1989. – Vol. 37, №8. – P. 2091-2102.

Price M.L.P., Guida, W.C., Jackson, T.C. et al. // Bioorg. Med. Chem. Lett. – 2003. – Vol. 13. – P. 107-110.

Vaisburg A., Paquin I., Bernstein N. et al. // Bioorg. Med. Chem. Lett. – 2007. – Vol. 17. – P. 6729-6733.

Ogawva K., Yamawakil I.I., Matsusital Y.I. et al. // Eur. J. Med. Chem. – 1993. – Vol. 28. – P. 769-781.

Пат. 3,475,429 (1969). – Заявл.: 28.05.1968. Опубл.: 28.10.1969.

Пат. 4,835,157 (1989). – Заявл.: 15.03.1988. Опубл.: 30.05.1989.

Ivachtchenko A.V., Kovalenko S.M., Tkachenko O.V., Parkhomenko O.O. // J. Comb. Chem. – 2004. – Vol. 6, №4. – Р. 573-583.

Пат. US6262058 B1 (2001). – Заявл.: 03.03.2001. Опубл.: 17.07.2001.

Бактеріологічний контроль поживних середовищ. Інформаційний лист МОЗ України №05.4.1/1670. – К., 2001.

Методичні рекомендації «Вивчення специфічної активності антимікробних лікарських засобів». – К., 2004. – 38 с.

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