Three-dimensional quantitative structure-activity relationship of the opioid antagonist with potent anorectant activity of 3,4-dimethyl-4-(3-hydroxyphenyl) piperidine

A series of 3,4-dimethyl-4-(3-hydroxyphenyl) piperidine opioid antagonists with varying substituents on the nitrogen were evaluated for their effect o n food consumption in obese Zucker rats. In developing three-dimensional qu antitative structure-activity relationship (3D-QSAR) studies for this serie s of opioid antagonists, different structure alignments have been tested to predict the anorectant activities. The interaction energies between molecu les and the probe atom were then correlated with anorectant activity using partial least squares (PLS) method. The steric and electrostatic features o f the 3D-QSAR were presented in the form of standard deviation coefficient contour maps of steric and electrostatic fields. The results showed that 3D -QSAR results are much better than the results obtained by 2D-QSAR.