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

Authors

  • O. V. Tkachenko National University of Pharmacy, Ukraine
  • S. V. Vlasov National University of Pharmacy, Ukraine
  • S. M. Kovalenko National University of Pharmacy, Ukraine
  • I. O. Zhuravel’ National University of Pharmacy, Ukraine
  • V. P. Chernykh National University of Pharmacy, Ukraine

DOI:

https://doi.org/10.24959/zofh.17.910

Keywords:

thiophene, pyrimidine, aromatic compounds, amides, antimicrobial substances

Abstract

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.

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Published

2013-12-02

How to Cite

(1)
Tkachenko, O. V.; Vlasov, S. V.; Kovalenko, S. M.; Zhuravel’, I. O.; Chernykh, V. P. Synthesis and the Antimicrobial Activity 1-N-Alkylated Derivatives of 3-N-Substituted 1H-thieno[3,2-d]pirimidine-2,4-Diones. J. Org. Pharm. Chem. 2013, 11, 15-21.

Issue

Vol. 11 No. 4(44) (2013)

Section

Original Researches

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Copyright (c) 2013 National University of Pharmacy

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