Quantitative structure-activity relationship of 4,5-diphenyl-2-(substituted thio)-1H-imidazoles as the inhibitors of acyl CoA: cholesterol acyltransferase.
Indian J Biochem Biophys
;
1998 Jun; 35(3): 179-83
Artigo
em Inglês
| IMSEAR
| ID: sea-28358
ABSTRACT
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.
Texto completo:
DisponíveL
Índice:
IMSEAR (Sudeste Asiático)
Assunto principal:
Ratos
/
Relação Estrutura-Atividade
/
Ureia
/
Microssomos Hepáticos
/
Desenho de Fármacos
/
Esterol O-Aciltransferase
/
Inibidores Enzimáticos
/
Imidazóis
/
Animais
Tipo de estudo:
Estudo prognóstico
Idioma:
Inglês
Revista:
Indian J Biochem Biophys
Ano de publicação:
1998
Tipo de documento:
Artigo
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