Abstract: X-ray crystallography and computer-assisted conformational analysis and computer graphics studies were performed for seven Fentanyl-type potent agonist of opiate receptor. The results obtained demonstrate that there is a good agreement between the experimentally determined (by X-ray) and the calculated (by DPCILO) conformation of Fentanyl derivatives. The orientation of the N-phenylpropanamide with respect to piperidine ring plays an important role in the binding of Fentanyl-type analgeties to the opiate receptor.
When the N-phenethyl substituent is the antiperiplanar conformation and torsion angle (C_(11)—C_(12)—N_(15)—C(16)) is about 100°, Fentanyl derivatives may interact equally well with the recetor. On the basis of conformational analysis and molecular graphics fit the model for the requirements of the receptor has also been discussed.