MTD-comsia modelling of HMG-CoA reductase inhibitors

The 3D quantitative structure-activity relationship for a series of hy- droxymethylglutaryl-CoA (HMG-CoA) reductase inhibitors based on the pyr- rolylethyl-tetrahydropyranone scaffold was examined using the Minimal Topo- logical Difference (MTD) method and comparative molecular similarity index analysis (CoMSIA). The studied compounds were of the tetrahydro-4-hydroxy- -6-(2-(1H-pyrrol-1-yl)ethyl)-2H-pyran-2-one type. In clinical practice, HMG- -CoA reductase inhibitors are usually referred to by the generic name statins. The analysis performed using the MTD method showed that voluminous sub- stituents produce a significant biological activity ( 2 CV R = 0.677 > 0.5; SEECV = = 0.319), while the CoMSIA method added useful information regarding the influence of the steric, electrostatic, hydrophobic, hydrogen bond donor, and acceptor properties on biological activity ( 2 CV R = 0.60; r 2 = 0.98).