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.
D Passarella, A Barilli, S M N Efange, E Elisabetsky, M B Leal, G Lesma, V M Linck, D C Mash, M Martinelli, I Peretto, A Silvani, B Danieli
Natural product research July 10, 2006 DOI: 10.1080/14786410500160645 via PubMed
Summary
AI-generated from the abstractA microwave-assisted chemical reaction was used to create a key intermediate for synthesizing ibogaine analogues. One analogue, a hydroxymethyl indolyl derivative, showed promising binding to dopamine, serotonin, and opioid receptors in lab tests and reduced withdrawal symptoms in mice. Simplifying the ibogaine molecule appears to be a useful strategy for designing new compounds to treat addiction withdrawal.
Study at a glance
| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Mice |
| Intervention | hydroxymethyl 7-indolyl-2-aza-bicyclo[2.2.2]oct-2-ene (14) |
| Keywords | Addiction treatment Withdrawal management Substance abuse therapy Drug recovery Dependency treatment |
| Citations | 4 |
| Key finding | A simplified ibogaine analogue, hydroxymethyl 7-indolyl-2-aza-bicyclo[2.2.2]oct-2-ene, showed an antiwithdrawal effect in mice and a binding profile toward dopamine, serotonin, and opioid receptors. |
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.