Deconstructing 14-phenylpropyloxymetopon: minimal requirements for binding to mu opioid receptors.
Bioorg Med Chem
; 20(14): 4556-63, 2012 Jul 15.
Article
en En
| MEDLINE
| ID: mdl-22677527
ABSTRACT
A series of phenylpropyloxyethylamines and cinnamyloxyethylamines were synthesized as deconstructed analogs of 14-phenylpropyloxymetopon and analyzed for opioid receptor binding affinity. Using the Conformationally Sampled Pharmacophore modeling approach, we discovered a series of compounds lacking a tyrosine mimetic, historically considered essential for µ opioid binding. Based on the binding studies, we have identified the optimal analogs to be N-methyl-N-phenylpropyl-2-(3-phenylpropoxy)ethanamine, with 1520 nM, and 2-(cinnamyloxy)-N-methyl-N-phenethylethanamine with 1680 nM affinity for the µ opioid receptor. These partial opioid structure analogs will serve as the novel lead compounds for future optimization studies.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Morfolinas
/
Receptores Opioides mu
/
Etilaminas
Tipo de estudio:
Prognostic_studies
Idioma:
En
Año:
2012
Tipo del documento:
Article