3D-QSAR studies of orvinol analogs as kappa-opioid agonists.
Orvinols are potent analgesics that target opioid receptors. However, their analgesic mechanism remains unclear and no significant preference for subtype opioid receptor has been achieved. In order to find new orvinols that target the kappa-receptor, comparative 3D-QSAR studies were performed on 26 orvinol analogs using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). The best predictions for the kappa-receptor were obtained with the CoMFA standard model (q2 = 0.686, r2 = 0.947) and CoMSIA model combined steric, electrostatic, hydrophobic, and hydrogen bond donor/acceptor fields (q2 = 0.678, r2 = 0.914). The models built were further validated by a test set made up of seven compounds, leading to predictive r2 values of 0.672 for CoMFA and 0.593 for CoMSIA. The study could be helpful for designing and prepare new category kappa-agonists from orvinols.
Department of Medicinal Chemistry, School of Pharmacy, Fudan University, 138 Yixueyuan Road, Shanghai, 200032, People's Republic of China.
Wei
W
Li
Yun
Y
Tang
Qiong
Q
Xie
Wei
W
Sheng
Zhui-Bai
ZB
Qiu
D000701:Analgesics, Opioid / Q000737:chemistry; D009294:Narcotics / Q000819:agonists; D021281:Quantitative Structure-Activity Relationship; D017473:Receptors, Opioid, kappa / Q000819:agonists*
D000701:Analgesics, Opioid; D009294:Narcotics; D017473:Receptors, Opioid, kappa