2D Quantitative structure-activity relationship studies on a series of cholesteryl ester transfer protein inhibitors

Bioorg Med Chem. 2007 Sep 15;15(18):6242-52. doi: 10.1016/j.bmc.2007.06.021. Epub 2007 Jun 13.

Abstract

Coronary heart disease (CHD) is one of the major causes of human death. The most successful therapeutic approach available is based on the reduction of low density-lipoprotein cholesterol (LDL-C). However, it is believed that the next paradigm in CHD treatment will rely on increased HDL-C levels. One of the most promising strategies for this goal is the inhibition of cholesteryl ester transfer protein (CETP). In the present work, robust classical 2D QSAR (r(2)=0.76, q(2)=0.72) and hologram QSAR (r(2)=0.88, q(2)=0.70) models were developed for a series of 85 CETP inhibitors (N-N-disubstituted trifluoro-3-amino-2-propanol derivatives). These models are complementary in nature and highlight important structural features for the design of novel CETP inhibitors with improved potency.

MeSH terms

  • 1-Propanol / chemistry
  • 1-Propanol / pharmacology*
  • Cholesterol Ester Transfer Proteins / antagonists & inhibitors*
  • Cholesterol Ester Transfer Proteins / metabolism
  • Cholesterol Esters / metabolism*
  • Lipoproteins, HDL / metabolism
  • Lipoproteins, LDL / metabolism
  • Models, Molecular
  • Molecular Structure
  • Quantitative Structure-Activity Relationship*
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Cholesterol Ester Transfer Proteins
  • Cholesterol Esters
  • Lipoproteins, HDL
  • Lipoproteins, LDL
  • 1-Propanol