| Abstract: | The semiempirical self-consistent field MO (CNDO /2) calculations have been undertaken for 13 compounds involving 3-methyl-fentanyl and its analogs. Various quantum chemical indices were obtained. The relationships between the biological activity and quantum chemical indices of molecules of these compounds were investigated and it was found that there are remarkable relationships between the activity and some important quantum chemical indices such as the α-electron density of β substituent and the electron density of piperidyl nitrogen. The nature of interaction between the analgesics' molecule and the receptor was discussed on the basis of the relationships between the activity and quantum chemical indices and it was proposed that the β-substituent functions not only as a hydrophobic group, but also its electronic property has important effect on the activity. It may act as an electron acceptor and form acceptor–donor complex with receptor through the charge transfer process. The piperidyl nitrogen interacts with receptor forming quaternary ammonium ion and acting as positive charge center, and its electron density also has an important effect on the activity. The amide oxygen and nitrogen may be other active centers which function as donors when they interact with the receptor. The influence on activity through introduction of the hydroxyl group to the β-position of the 1-substituent of the piperdyl ring has also been discussed. |
