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.
Daniele Passarella, A Barilli, Simon M. N. Efange, E Elisabetsky, M B Leal, Giordano Lesma, V M Linck, Deborah C. Mash, Marisa Martinelli, I Peretto, Alessandra Silvani, Bruno Danieli
Natural Product Research July 10, 2006 DOI: 10.1080/14786410500160645 (opens in new tab)
Study at a glance
AI-extracted from the abstract| 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 Addiction therapy Addiction medicine Addiction challenges Overcoming addiction Pharmaceutical research Compound identification Drug development New drug discovery Therapeutic innovation New treatments Creating treatments Receptor binding Drug action Neuropharmacology Mechanism of action Drug effects Dopamine receptors Serotonin receptors Opioid receptors Medicinal chemistry Drug design Synthetic chemistry Pharmaceutical chemistry Organic chemistry Precise chemical synthesis Ibogaine-inspired compounds Hydroxymethyl indolyl derivative |
| Citations | 4 |
| Key findings | 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.