ISSN:
0192-8651
Keywords:
Computational Chemistry and Molecular Modeling
;
Biochemistry
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
,
Computer Science
Notes:
Conformational energy calculations using the empirical MM2 (molecular mechanics II) and semiempirical quantum mechanical PCILO (perturbative configuration interaction using localized orbitals) methods are reported for various prodine derivatives. These include 3-demethylprodine, α-prodine, β-prodine, the α-2-methyl derivative, α-promedol, the γ-2,3-dimethyl derivative, and γ-isopromedol. The results are consistent with all of the compounds activating the opiate receptor in a phenyl equatorial conformation with optimum activity resulting from a particular orientation of the phenyl and propionoxyl groups. In disagreement with previous limited experimental data, α-promedol is found to prefer a phenyl equatorial conformer. It is confirmed that, of the two mirror image phenyl equatorial conformers that are preferred for 3-demethylprodine, the more active prodines antipodes consistently prefer the one in which the phenyl orientation is the opposite (mirror image) of that found in morphine and in the preferred conformer of the morphine-like (+)-phenylmorphan. This is a possible molecular basis for the nonmorphine-like effects that occur with the introduction of a phenyl meta hydroxyl into some prodine derivatives. It is also suggested that the less active prodine antipodes, which have a morphine-like phenyl orientation, may act in a morphine-like manner at opiate receptors.
Additional Material:
8 Ill.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/jcc.540050602
