Conformational study of fentanyl and its analogs. 3. Conformational space and electronic properties of carfentanil, 3-carbomethoxy fentanyl and CH-fentanyl

摘要

The conformational space and electronic properties of the CH-fentanyl, a postulated antagonist of the fentanyl class of opiates, have been investigated by molecular mechanics (MM2) and quantum mechanics (PM3) methods. It has been found that reduced proton affinity of the amide oxygen (i.e., reduced electron density in this region) might be the major reason for the reduced activity of CH-fentanyl compared to fentanyl. Carfentanil and 3-carbomethoxy fentanyl have also been studied in order to determine the location requirements for the high electron density region, which is believed to be one of the modulators of receptor activation.