Nature-inspired indolyl-2-azabicyclo[2.2.2]oct-7-ene derivatives as promising agents for the attenuation of withdrawal symptoms: synthesis of 20-desethyl-20-hydroxymethyl-11-demethoxyibogaine.
Nat Prod Res
; 20(8): 758-65, 2006 Jul 10.
Article
em En
| MEDLINE
| ID: mdl-16753910
ABSTRACT
Microwave assisted Diels-Alder cycloaddition of 5-Br-N-benzylpyridinone (2) with methyl acrylate is described to gain an easy access to 7-bromo-2-benzyl-3-oxo-2-aza-5 or 6-carbomethoxy bicyclo[2.2.2]oct-7-enes (3)-(6). The preparation of the ibogaine analogue 20-desethyl-(20-endo)-hydroxymethyl-11-demethoxyibogaine (17) is described by stereoselective hydrogenation of the C(7)-C(8) double bond. Biological evaluation showed an interesting in vitro binding profile toward dopamine transporter, serotonin transporter and opioid receptor systems accompanied by an antiwithdrawal effect in mice for hydroxymethyl 7-indolyl-2-aza-bicyclo[2.2.2]oct-2-ene (14). The simplification of the ibogaine structure appears as a promising approach toward the design of compounds that could reduce the withdrawal symptoms.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Tipo de estudo:
Diagnostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2006
Tipo de documento:
Article