ISSN:
1573-4951
Keywords:
Pseudoreceptor modeling
;
Opiate molecular modeling
;
Quantitative structure-activity relationships
;
QSAR
;
Dielectric constants
;
Docking
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
Notes:
Summary Thirteen 4,5-epoxymorphinan μ 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 α-isomorphine, the geometric isomer B/C trans-morphine, and the 8-position-substituted γ-isomorphine were successes in the n-decane condition, whereas the ethanol condition produced the substituted codeine derivatives dihydroco-deinone 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.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00129425
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