Synthesis and the antimicrobial activity of ethyl 3-alkyl-2-(alkylthio)-5-methyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidine-6-carboxylate derivatives

Authors

  • S. V. Vlasov National University of Pharmacy, Ukraine
  • V. P. Chernykh National University of Pharmacy, Ukraine
  • T. P. Osolodchenko SI «Institute of microbiology and immunology n.I.I.Mechnikov NAMS», Ukraine

DOI:

https://doi.org/10.24959/nphj.15.2070

Keywords:

thiophene, pyrimidine, mercaptans, alkylation, cyclization

Abstract

The effective method for the synthesis of ethyl 3-alkyl-5-methyl-4-oxo-2-thioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidine-6-carboxylate derivatives by interaction of diethyl 3-methyl-5-{[(methylsulfanyl)carbothioyl]amino}thiophene-2,4-dicarboxylate with low aliphatic amines in the 2-propanol medium has been developed. The conditions proposed facilitate isolation and perceptibly improve the yields of the target thiones. The further modification of ethyl 3-alkyl-5-methyl-4-oxo-2-thioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidine-6-carboxylate has been performed by alkylation with chloroacetamides and 3-aryl-5-(chloromethyl)-1,2,4-oxadiazoles (DMF-triethylamine). The structure of the compounds obtained has been confirmed using the NMR spectroscopic methods; the products of alkylation have the signals of the carbethoxy group as two signals in the ranges of 1.27-1.30 ppm (3H, t) and 4.24-4.29 (2H, q), and the signal of SCH2 protons in the range of 4.22-4.93 ppm. The study of the antimicrobial activity for the functionalized derivatives of thieno[2,3-d]pyrimidine, the corresponding ethyl 3-alkyl-5-methyl-2-({2-[arylamino]-2-oxoethyl}thio)-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidine-6-carboxylates and ethyl 3-alkyl-5-methyl-4-oxo-2-{[(3-aryl-1,2,4-oxadiazol-5-yl)methyl]thio}-3,4-dihydrothieno[2,3-d]pyrimidine-6-carboxylate has shown their moderate antimicrobial properties, while for some compounds with the n-butyl substituent at position 3 possess the high inhibitory activity against Candida albicans fungi growth.

Author Biographies

S. V. Vlasov, National University of Pharmacy

Доцент кафедры органической химии

V. P. Chernykh, National University of Pharmacy

Ректор Национального фармацевтического Университета

T. P. Osolodchenko, SI «Institute of microbiology and immunology n.I.I.Mechnikov NAMS»

Завідувач лабораторії біохімії живильних середовищ

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Published

2015-09-11

Issue

Section

Synthesis and Analysis of Biologically Active Substances