Синтез та антимікробна активність 1-n-алкілованих похідних 3-n-заміщених 1н-тієно [3,2-d]піримідин-2,4-діонів

• Дата: 2013
• Автори: Tkachenko, O. V., Vlasov, S. V., Kovalenko, S. M., Zhuravel’, I. O., Chernykh, V. P.
• Формат: Стаття
• Мова: English
• Опубліковано: National University of Pharmacy 2013
• Теми: thiophene; pyrimidine; aromatic compounds; amides; antimicrobial substances; UDC 615.28; 542.951.1; 661; 185.222.13; 547.853.3; 547.732; тиофен; пиримидин; ароматические соединения; амиды; противомикробные средства; УДК 615.28; тіофен; піримідин; ароматичні сполуки; аміди; антимікробні засоби
• Онлайн доступ: https://ophcj.nuph.edu.ua/article/view/ophcj.13.763
• Назва журналу: Journal of Organic and Pharmaceutical Chemistry

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.