Modeling of the growth hormone secretagogue receptor antagonistic activity using chemometric tools.
A quantitative structure-activity relationship (QSAR) study has been carried out on growth hormone secretagogue receptor antagonistic activity of the derivatives of 2,4-diaminopyrimidine. To obtain significant QSARs, the approaches involving the non-parametric such as Fujita-Ban, and the parametric based on physicochemical and DRAGON descriptors in Hansch type of analysis have been employed. The Fujita-Ban approach, however, was constrained to 18 compounds only due to a limited number of substituents appeared at varying positions. The derived contributions of different substituents and the parent moiety were used to identify the potential congeners. The physicochemical model of Hansch was subsequently used to interpret the type of interactions involved between the receptor sites and varying positions of these compounds. The study, employing DRAGON descriptors in Hansch approach was also carried out on this data set to discuss the prevailing interactions in terms of topological descriptors. The derived highest significant model was discussed to delineate the type of interactions involved and suggestions have been made for different alterations to lead to further potential compounds of the series.
Sharma
Susheela
S
Department of Engineering Chemistry, Sobhasaria Engineering College, Sikar 332 021, India.
Sharma
B K
BK
Pilania
P
P
Singh
P
P
Prabhakar
Y S
YS
D000818:Animals; D006801:Humans; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D015394:Molecular Structure; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D021281:Quantitative Structure-Activity Relationship; D054440:Receptors, Ghrelin / Q000037:antagonists & inhibitors*
D011743:Pyrimidines; D054440:Receptors, Ghrelin; C017205:2,4-diaminopyrimidine