QSAR study of the role of hydrophobicity in the activity of HMGR inhibitors.

The 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR) inhibitory activity of 7-(aryl/biphenyl)-6-heptenoic acids was quantitatively analysed using hydrophobicity, van der Waals volume and electronic parameters. The activity was primarily a function of hydrophobicity, and was well correlated with the hydrophobicity of ortho and meta substituents on the aryl/biphenyl moiety. The electronic properties of para substituents on the aryl/biphenyl ring influenced the inhibition. Our equations predict that substituents with positive polar and sigma and negative resonance constants might lead to better inhibition.