188895-96-7Relevant articles and documents
Epiboxidine and novel-related analogues: A convenient synthetic approach and estimation of their affinity at neuronal nicotinic acetylcholine receptor subtypes
Rizzi, Luca,Dallanoce, Clelia,Matera, Carlo,Magrone, Pietro,Pucci, Luca,Gotti, Cecilia,Clementi, Francesco,De Amici, Marco
, p. 4651 - 4654 (2008)
Racemic exo-epiboxidine 3, endo-epiboxidine 6, and the two unsaturated epiboxidine-related derivatives 7 and 8 were efficiently prepared taking advantage of a palladium-catalyzed Stille coupling as the key step in the reaction sequence. The target compounds were assayed for their binding affinity at neuronal α4β2 and α7 nicotinic acetylcholine receptors. Epiboxidine 3 behaved as a high affinity α4β2 ligand (Ki = 0.4 nM) and, interestingly, evidenced a relevant affinity also for the α7 subtype (Ki = 6 nM). Derivative 7, the closest analogue of 3 in this group, bound with lower affinity at both receptor subtypes (Ki = 50 nM for α4β2 and Ki = 1.6 μM for α7) evidenced a gain in the α4β2 versus α7 selectivity when compared with the model compound.
[3 + 2] Cycloaddition of Nonstabilized Azomethine Ylides. 8. An Efficient Synthetic Strategy for Epiboxidine
Pandey, Ganesh,Sahoo, Akhila K.,Gadre, Smita R.,Bagul, Trusar D.,Phalgune, Usha D.
, p. 4990 - 4994 (2007/10/03)
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Synthesis and nicotinic activity of epiboxidine: An isoxazole analogue of epibatidine
Badio, Barbara,Garraffo, H. Martin,Plummer, Carlton V.,Padgett, William L.,Daly, John W.
, p. 189 - 194 (2007/10/03)
Synthetic (±)-epiboxidine (exo-2-(3-methyl-5-isoxazolyl)-7-azabicyclo[2.2.1]heptane) is a methylisoxazole analog of the alkaloid epibatidine, itself a potent nicotinic receptor agonist with antinociceptive activity. Epiboxidine contains a methylisoxazolyl ring replacing the chloropyridinyl ring of epibatidine. Thus, it is also an analog of another nicotinic receptor agonist, ABT 418 ((S)-3-methyl-5-(1-methyl-2-pyrrolidinyl)isoxazole), in which the pyridinyl ring of nicotine has been replaced by the methylisoxazolyl ring. Epiboxidine was about 10-fold less potent than epibatidine and about 17-fold more potent than ABT 418 in inhibiting [3H]nicotine binding to α4β2 nicotinic receptors in rat cerebral cortical membranes. In cultured cells with functional ion flux assays, epiboxidine was nearly equipotent to epibatidine and 200-fold more potent than ABT 418 at α3β(4(5)) nicotinic receptors in PC12 cells. Epiboxidine was about 5-fold less potent than epibatidine and about 30-fold more potent than ABT 418 in TE671 cells with α1β1γδ nicotinic receptors. In a hot-plate antinociceptive assay with mice, epiboxidine was about 10-fold less potent than epibatidine. However, epiboxidine was also much less toxic than epibatidine in mice.
