Quantitative structure-activity relationship of 4,5-diphenyl-2-(substituted thio)-1H-imidazoles as the inhibitors of acyl CoA: cholesterol acyltransferase.
A quantitative structure-activity relationship (QSAR) analysis of 4,5-diphenyl-2-(substituted thio)-1H-imidazoles as the potential inhibitors of acyl CoA: cholesterol acyltransferase is presented with a view to reflect upon the parametric requirement of various substitutions. For this purpose the van der Waals volume, Vw which is the measure of molecular bulk/size of substituents present at R1- and R2-positions has emerged as the befitting correlative parameter. A number of correlations obtained amongst different subclasses of the title compounds have helped in ascertaining the relative importance of X-substituents and the role of Vw(R1) and Vw(R2). Finally, a significant correlation between the sum of van der Waals volume of R1- and R2-substituents, sigma Vw and biological activities of the entire series was also derived. From the resulting parabolic QSAR equation, an optimum molecular bulk of 1.846 x 10(2) A3 leading to the highest potent compound of the series, specially among those congeners which have X = -NH-, was predicted. This finding has, therefore, hinted at the existence of a cavity, capable of accommodating the maximum steric bulk, on to the receptor.
Singh
P
P
Department of Chemistry, S.K. Government College, Sikar, India.
Kumar
R
R
D000818:Animals; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry; D007093:Imidazoles / Q000737:chemistry*; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D051381:Rats; D002785:Sterol O-Acyltransferase / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014508:Urea / Q000031:analogs & derivatives
D004791:Enzyme Inhibitors; D007093:Imidazoles; D014508:Urea; D002785:Sterol O-Acyltransferase