Synthesis, screening and QSAR studies of 3-benzoyl-2-oxo/thioxo-1,2,3,4-tetrahydro-pyrimidine analogues as antibacterial agents

Abstract

The purpose of this study was to synthesize several 3-benzoyl-5-acyl-6-methyl-4-substituted-2-oxo/thioxo-1,2,3,4-tetrahydropyrimidines, evaluate them for their antibacterial activity and to establish correlation between the activity and physicochemical properties. 5-Acyl-6-methyl-4-substituted-2-oxo/thioxo-1,2,3,4-tetrahydropyrimidines (A) were synthesized by cyclocondensation reaction between appropriate aldehyde, acetoacetate and urea/thiourea in presence of aluminium chloride and hydrochloric acid which upon treatment with benzoyl chloride in presence of pyridine in benzene furnish the title compounds (1-28). The structures of all title compounds have been confirmed on the basis of their analytical, IR and NMR spectral data. The title compounds have been tested for antibacterial activity against Staphylococcus aureus. The compounds were divided into training and test sets. A quantitative structure activity relationship study was made using various descriptors. Several statistical expressions were developed using stepwise multiple linear regression analysis. The best quantitative structure activity relationship model was further cross validated. The study revealed that total positive partial charge (PC+) and total polar negative Van der Waals surface area (Q_VSA_PNEG) contributes negatively where as contribution of Van der Waals surface area to molar refractivity (SMR_VSA7) contributes positively to the antibacterial activity. The compounds with improved antibacterial potential can be successfully designed with selected quantitative structure activity relationship model.

KEY WORDS: 2-Oxo/thioxo-1,2,3,4-tetrahydropyrimidines, Antibacterial, QSAR

Bull. Chem. Soc. Ethiop. 2008, 22(3), 391-402.