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.
Medical Chemistry Division, Central Drug Research Institute, Lucknow, India.
Y S
YS
Prabhakar
A K
AK
Saxena
M J
MJ
Doss
D055598:Chemical Phenomena; D002627:Chemistry, Physical; D006538:Heptanoic Acids / Q000494:pharmacology; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D013329:Structure-Activity Relationship
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors