2D Quantitative structure-activity relationship studies on a series of cholesteryl ester transfer protein inhibitors.
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.
Castilho
Marcelo S
MS
Laboratório de Bioinformática e Modelagem Molecular, Faculdade de Farmácia, Universidade Federal da Bahia, Campus Universitário de Ondina, 40170-290 Salvador, BA, Brazil. castilho@ufba.br
Guido
Rafael V C
RV
Andricopulo
Adriano D
AD
D000433:1-Propanol / Q000737:chemistry / Q000494:pharmacology*; D053480:Cholesterol Ester Transfer Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002788:Cholesterol Esters / Q000378:metabolism*; D008075:Lipoproteins, HDL / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D008958:Models, Molecular; D015394:Molecular Structure; D021281:Quantitative Structure-Activity Relationship; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D000433:1-Propanol