1 - Benzyl-4 - Methoxycarbonyl Fentanyl Class Of Compounds, Synthesis And Comparative Molecular Field Analysis

Fentanyl as a new kind of powerful effect analgesic medicine was reported for the first time by Janssen in 1960s; hereafter the study on this kind of drug aroused the enormous interest. Fentanyl is famous as the highly effective anaesthesia analgesic medicine, and has the character of the analgesia high intensity, the rapid function and the short duration. Some 4-substitution the fentanyl derivatives, for example 4-methoxycarbonyl fentanyl and 4-methoxymethyl fentanyl are one of strongest types of analgesia activity, among which 4-methoxycarbonyl fentanyl analgesia activity for morine 10,031 times. Sufentanil and alfentanil develops from this kind of derivatives had been applied to the clinical as stability analgesia and the anaesthesia technique. Because of the little influence on the cardiovascular system, it was applicated in the surgery of the heart to widely.In our article, 3D-QSAR on fentanyl was studied using computer aided drug design, in this program CoMFA was the main method. Pharmacoore screening with piperdinecarboxamides derivatives using GALAHAD study and CoMFA study based on these pharmacoores were also achieved meanwhile. According literature, a kind of compounds about fentanyl was prepared passing the process of addition, hybridization, etherification, and acylation in our experiment. The yield was increase to three times because of the optimizing on the experiment condition. Otherwise, some new methods were used in our experiment, for example, microwave catalysis, orthogonal experiment. The yield was enhanced from 55.6% to 79% and the reaction time was shorted from 72h to 1.5h. The thionation of carfentanyl was achieved using P₂S₅ in our experiment.