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

• Published in: Bioorganic & medicinal chemistry 2007-09, Vol.15 (18), p.6242-6252
• Main Authors: Castilho, Marcelo S., Guido, Rafael V.C., Andricopulo, Adriano D.
• Format: Article
• Language: English
• Subjects: 1-Propanol - chemistry; 1-Propanol - pharmacology; Biological and medical sciences; Cardiovascular system; CETP; Cholesterol Ester Transfer Proteins - antagonists & inhibitors; Cholesterol Ester Transfer Proteins - metabolism; Cholesterol Esters - metabolism; Coronary heart disease; Inhibitors; Lipoproteins, HDL - metabolism; Lipoproteins, LDL - metabolism; Medical sciences; Miscellaneous; Models, Molecular; Molecular Structure; Pharmacology. Drug treatments; QSAR; Quantitative Structure-Activity Relationship; Stereoisomerism; Structure-Activity Relationship; Trifluoro-3-amino-2-propanol derivatives
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2007.06.021

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. 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.