European Journal of Medicinal Chemistry 2006-02-01

QSAR study of 4-phenylpiperidine derivatives as mu opioid agonists by neural network method.

Xing-hai Wang, Yun Tang, Qiong Xie, Zhui-bai Qiu

Index: Eur. J. Med. Chem. 41(2) , 226-32, (2006)

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Abstract

A nonlinear QSAR study was conducted on a series of 4-phenylpiperidine derivatives (4PPs) acting as mu opioid agonists by three-layer back-propagation neural network (NN) method. At first a variety of molecular descriptors were calculated and then selected with two-stage least squares combining partial least squares (PLS) method. The selected four molecular descriptors, out of 292 ones, were correlated with the known analgesic activities of 38 4PPs by NN method. The established QSAR model was further validated by five additional 4PPs, as an external testing set. Moreover, a pharmacophore model was hypothesized based on the results, which would be helpful for structural optimization of 4PPs.