Development of pharmacophoric model of condensed pyridine and pyrimidine analogs as hydroxymethyl glutaryl coenzyme A reductase inhibitors.
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2006-02-08
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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.
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Saxena M, Soni LK, Gupta AK, Wakode SR, Saxena AK, Kaskhedikar SG. Development of pharmacophoric model of condensed pyridine and pyrimidine analogs as hydroxymethyl glutaryl coenzyme A reductase inhibitors. Indian Journal of Biochemistry & Biophysics. 2006 Feb; 43(1): 32-6