Studies of cannabinoid-1 receptor antagonists for the treatment of obesity: hologram QSAR model for biarylpyrazolyl oxadiazole ligands.
Hologram QSAR studies were conducted on a series of 60 training set of cannabinoid-1 receptor (CB(1)) antagonists. Significant cross-validated correlation coefficients (q(2)=0.763) and noncross-validated correlation coefficients (r(2)=0.897) were obtained. The model was then employed to predict the biological activities of 15 test set compounds, and a good agreement between the experimental and predicted values was verified exhibiting a powerful predictable capability of this model (q(pred)(2)=0.868). Contribution map shows that 1,2,4-trizole and cyclopropane moieties make big contributions for the activities. Both the HQSAR model and analysis from the contribution map should be useful for the further design of novel structurally related CB(1) antagonists.
Ye
Mao
M
Burnham Institute for Medical Research, La Jolla, CA 92037, USA. maoye@burnham.org
Dawson
Marcia I
MI
D003521:Cyclopropanes; D015195:Drug Design; D008024:Ligands; D009765:Obesity / Q000188:drug therapy*; D010069:Oxadiazoles / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors*; D014230:Triazoles
D003521:Cyclopropanes; D008024:Ligands; D010069:Oxadiazoles; D043884:Receptor, Cannabinoid, CB1; D014230:Triazoles; C045575:1,2,4-triazole