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

Abstract

An effective approach for synthesis of 5-methyl-3-phenyl-6-(5-phenyl-1,3,4-oxadiazol-2-yl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione by 1,1’-carbonyldiimidazole promoted interaction of 5-methyl-2,4-dioxo-3-phenyl-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidine-6-carboxylic acid with benzohydrazide has been developed. The procedure also includes cyclization of N’-benzoyl-5-methyl-2,4-dioxo-3-phenyl-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidine-6-carbohydrazide obtained by boiling in phosphorous oxychloride and further hydrolysis of the chlorine atom at position 2 of the thieno[2,3-d]pyrimidine system. Alkylation of the assembly of two heterocyclic units obtained with benzyl chlorides, chloroacetamides, and 5-(chloromethyl)-3-aryl-1,2,4-oxadiazoles has allowed obtaining of 1-alkyl-5-methyl-3-phenyl-6-(5-phenyl-1,3,4-oxadiazol-2-yl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-diones. The structures of the compounds obtained have been confirmed by the 1 H NMR, chromato-mass spectral and elemental microanalysis data. The results of the screening performed by the agar diffusion method (“well method”) have shown the absence of the antimicrobial activity for 1-benzyl-5-methyl-3-phenyl-6-(5-phenyl-1,3,4-oxadiazol-2-yl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-diones and 2-[5-methyl-2,4-dioxo-3-phenyl-6-(5-phenyl-1,3,4-oxadiazol-2-yl)-3,4-dihydrothieno[2,3-d]pyrimidin-1(2H)-yl]-N-arylacetamides; but the activity for 1-{[3-aryl-1,2,4-oxadiazol-5-yl]methyl}-5-methyl-3-phenyl-6-(5-phenyl-1,3,4-oxadiazol-2-yl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-diones has been found. The compounds of this range appeared to be active against the strains of Staphylococcus aureus, Escherichia coli and Bacillus subtilis; the diameters of their growth inhibition zones were similar to those for the reference drugs Metronidazole and Streptomycin.