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.
Prabhakar
Y S
YS
Medical Chemistry Division, Central Drug Research Institute, Lucknow, India.
Saxena
A K
AK
Doss
M J
MJ
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