Synthesis, characterisation and antibacterial activity of thiadiazolopyrimidinones.

Abstract

Seven thiadiazolopyrimidinone hybrid derivatives were successfully synthesized in a three step reaction that involved synthesis of 5-substituted phenyl-1,3,4-thiadiazole-2-amines, condensation of the amines with DMF-DMA (dimethylformamide-dimethylacetal), and the [4+2] cycloaddition reaction of the imidoformamides and phenoxyketene. The DMF-DMA used in the second step was synthesized using sodium methoxide, DMF and dimethylsulfate (DMS). The synthesized compounds were all novel derivatives. Structural elucidation of all synthesized compounds was carried out using both 1D and 2D NMR spectroscopy together with mass spectrometry. All synthesized compounds were subjected to antibacterial testing against both Gram positive and Gram negative strains and showed excellent activity against Gram negative strains but no activity against Gram positive bacteria. In comparison to the two standards used, Levoflaxocin and Ciproflaxocin, compounds 3a (MBC = 0.19 μM) and 3e (MBC = 0.15-3.92 μM) showed better activity against Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumonia and Salmonella typhimurium while compounds 3b, 3d, 3g and 3h showed better activity than these standards for three of the four strains.