A pseudoreceptor docking study of 4,5-alpha-epoxymorphinans with a range of dielectric constants.
J Comput Aided Mol Des
; 6(2): 149-58, 1992 Apr.
Article
en En
| MEDLINE
| ID: mdl-1320664
ABSTRACT
Thirteen 4,5-epoxymorphinan mu agonists with established analgesic action were docked into an Asp-Lys-His-Phe pseudoreceptor complex under a range of distance-dependent dielectric conditions. The number of compounds with potential energies of the docked complexes that agreed in rank order with corresponding analgesic potencies was determined for each condition. Two dielectric conditions, n-decane (1.991) and ethanol (24.3), enabled the greatest number of compounds to relate to their pseudoreceptors with each having 9 and 8 successes respectively. Both of these conditions demonstrated unique influences on the types of structures that were successfully docked. For example, the morphine stereoisomer alpha-isomorphine, the geometric isomer B/C trans-morphine, and the 8-position-substituted gamma-isomorphine were successes in the n-decane condition, whereas the ethanol condition produced the substituted codeine derivatives dihydrocodeinone and dihydroxycodeinone. These findings emphasize the importance of dielectric influence when developing force-field modeled quantitative structure-activity relationships for a closely related homologous series.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Receptores Opioides
/
Morfinanos
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
J Comput Aided Mol Des
Asunto de la revista:
BIOLOGIA MOLECULAR
/
ENGENHARIA BIOMEDICA
Año:
1992
Tipo del documento:
Article