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

Abstract

The purpose of this study was to synthesize several 3-benzoyl-5-acyl-6-methyl-4-substituted-2oxo/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-1,2,3,4tetrahydropyrimidines (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.

Hantzsch-Type Dihydropyridines and Biginelli-Type Tetra-hydropyrimidines: A Review of their Chemotherapeutic Activities

“…The same research group also investigated the results using the QSAR approach and observed a good correlation between the structural features and biological activity. They concluded that molecules with a less positive partial charge and a negative polar Van der Waals surface area make a higher contribution rather than the ratio of Van der Waals surface area to molar refractivity (119). A substituted benzoyl methyl thio group located on the C-2 position of the THPM ring seemed to be effective in the antimicrobial activity, as effective as a moiety located on N-3 position.…”

Pyridine-based, microwave-assisted one-pot synthetic protocol for the synthesis of ethyl 3-substituted-4-oxo-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylates

“…This method represented a simple and efficient synthesis of complex molecules based upon one-pot, multi-component condensation reaction between thiourea/urea, appropriate aldehydes and b-ketoesters under strong acidic conditions [14,15]. Further, several new improved procedures for the classical method using Lewis acids, such as combination of aluminium chloride and hydrochloric acid (HCl) [16], BF 3 ÁOEt 2 [17], low-melting tartaric acidurea mixtures [9], metal triflates [18,19], zeolites [20], strong protic acids like HCl [21,22] and sulfuric acid (H 2 SO 4 ) [21] have been developed; also, microwave- [23] and ultrasonic-assisted methods [24] have been developed. Moreover, Friot et al [25] reported that S-methylthioimines or its iodide salts reacted with acrylic dienophiles or ketenes in the presence of triethylamine to give methylthiodihydropyrimidines/methylthiotetrahydropyrimidines with good yields.…”

Determination of Dissociation Constants of Some Novel Tetrahydropyrimidine Derivatives in Mixed Organic-Water System by Simple pH Measurement

“…The pyrimidine fragment is present in various biologically active compounds, many of which are used therapeutically [1][2][3]. Thus, much attention has been paid to derivatives of pyrimidines, including their hydrogenation products.…”