@article{APS3952,
author = {Wei Li and Xing-hai Wang and Choi-wan Lau and Yun Tang and Qiong Xie and Zhui-bai Qiu},
title = {Conformational re-analysis of (+)-meptazinol: an opioid with mixed analgesic pharmacophores},
journal = {Acta Pharmacologica Sinica},
volume = {27},
number = {9},
year = {2016},
keywords = {},
abstract = {Aim: To further investigate the analgesic pharmacophore of (+)-meptazinol.
Methods: Two different opioid pharmacophores, Pharm-I and Pharm-II, were established from structures of nine typical opiates and meperidine by using molecular modeling approaches according to their different structure activity relationship properties. They were further validated by a set of conformationally constrained arylpiperidines. Two conformers of (+)-meptazinol (Conformer-I and Conformer-II) detected in solution were then fitted into the pharmacophores, respectively, by Fit Atoms facilities available in SYBYL, a computational modeling tool kit for molecular design and analysis.
Results: Conformer-I fit Pharm-I from typical opiates well. However, Conformer-II fit none of these pharmacophores. Instead, it was found to be similar to another potent analgesic, benzofuro[2,3-c] pyridin-6-ol, whose pharmacophore was suggested to hold the transitional state between the two established pharmacophores. Unlike typical analgesics derived from 4-aryl piperidine (eg, meperidine) with one conformer absolutely overwhelming, the (+)-meptazinol exists in two conformers with similar amounts in solution. Furthermore, both conformers can not transform to each other freely in ordinary conditions based on our NMR results.
Conclusion: (+)-meptazinol was suggested to be an opioid with mixed analgesic pharmacophores, which may account for the complicated pharmacological properties of meptazinol.},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/3952}
}