title: Development of pharmacophoric model of condensed pyridine and pyrimidine analogs as hydroxymethyl glutaryl coenzyme A reductase inhibitors.
abstract: Quantitative structure-activity relationship (QSAR) has been established on a series of thirty-eight compounds of four different sets of condensed pyridine and pyrimidine analogs, for their hydroxymethyl glutaryl coenzyme (HMG-CoA) reductase inhibitor activity, in order to understand the essential structural requirement for binding with receptor, in terms of common biophoric and secondary sites employing APEX-3D software. Among several 3D pharmacophoric models with different sizes and arrangements, one model was selected based on r2 = 0.8, chance<0.001, match equivalent to 0.38 and all the 38 compounds were considered. The results suggest that hydrophobicity, hydrogen acceptor and optimum steric refractivity play a dominant role in the inhibition of HMG-CoA reductase. The information obtained from the present study can be used to design and predict more potent molecules as HMG-CoA reductase inhibitors, prior to their synthesis.
authors.affiliation: Molecular Modelling Study Group, CADD Laboratory, Department of Pharmacy Shri G S Institute of Technology and Science, Indore, M P, India.
authors.forename: M
authors.initials: M
authors.lastname: Saxena
authors.forename: Love K
authors.initials: LK
authors.lastname: Soni
authors.forename: Arun K
authors.initials: AK
authors.lastname: Gupta
authors.forename: S R
authors.initials: SR
authors.lastname: Wakode
authors.forename: A K
authors.initials: AK
authors.lastname: Saxena
authors.forename: S G
authors.initials: SG
authors.lastname: Kaskhedikar
mesh_terms: D015195:Drug Design; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D008956:Models, Chemical; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology; D021281:Quantitative Structure-Activity Relationship
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011725:Pyridines; D011743:Pyrimidines