3D-pharmacophore models for selective κ-opioid receptor antagonists
Selective K-opioid receptor antagonists are thought to play an important role in treatment of cocaine addiction, depression, psychosis and schizophrenia. To investigate the antagonistic mechanism and find selective and potent K-opioid antagonists, the threedimensional common feature pharmacophore model of Kopioid antagonists was generated by using the HipHop program of Catalyst software. The best pharmacophore model contained five chemical features: one positive ionizable group (PI), two hydrophobic groups (HY1 and HY2) and two hydrogen bond acceptors (HBA1 and HBA2). The model was capable of identifying high potent Kantagonists with other type opioid ligands. The results of our study should serve as a guide to elucidate the molecular mechanisms of K-opioid receptor and antagonists. In addition, they could also aid in the discovery of more selective and potent K-opioid antagonists that were candidates for new therapeutic agents.
Junjie Ding Xiaoqin Ding
Beijing Institute of Pharmaceutial Chemistry, Beijing, China
国际会议
武汉
英文
378-385
2010-09-01（万方平台首次上网日期，不代表论文的发表时间）