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{{Short description|Chemical compound}}
{{Drugbox
{{Drugbox
| IUPAC_name = (''1R'',''4S'',''6S'')-6-(3-Methylisoxazol-5-yl)-7-azabicyclo[2.2.1]heptane
| IUPAC_name = (''1R'',''4S'',''6S'')-6-(3-Methylisoxazol-5-yl)-7-azabicyclo[2.2.1]heptane
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<!--Identifiers-->
<!--Identifiers-->
| CAS_number = 188895-96-7
| CAS_number = 188895-96-7
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = XI646L2ARJ
| ATC_prefix =
| ATC_prefix =
| ATC_suffix =
| ATC_suffix =
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'''Epiboxidine''' is a chemical compound which acts as a [[partial agonist]] at neural [[nicotinic acetylcholine receptor]]s, binding to both the [[ganglion type nicotinic receptor|α3β4]] and the [[Alpha-4 beta-2 nicotinic receptor|α4β2]] [[nicotinic acetylcholine receptor#Subunits|subtypes]]. It was developed as a less toxic [[analog (chemistry)|analogue]] of the potent frog-derived [[alkaloid]] [[epibatidine]], which is around 200 times stronger than [[morphine]] as an [[analgesic]] but produces extremely dangerous toxic nicotinic [[adverse reaction|side effects]].
'''Epiboxidine''' is a chemical compound which acts as a [[partial agonist]] at neural [[nicotinic acetylcholine receptor]]s, binding to both the [[ganglion type nicotinic receptor|α3β4]] and the [[Alpha-4 beta-2 nicotinic receptor|α4β2]] [[nicotinic acetylcholine receptor#Subunits|subtypes]]. It was developed as a less toxic [[analog (chemistry)|analogue]] of the potent frog-derived [[alkaloid]] [[epibatidine]], which is around 200 times stronger than [[morphine]] as an [[analgesic]] but produces extremely dangerous toxic nicotinic [[adverse reaction|side effects]].


Epiboxidine is around one-tenth as potent as epibatidine as an α4β2 agonist, but has around the same potency as an α3β4 agonist. It has only one-tenth of the analgesic power of epibatidine, but is also much less toxic.<ref>{{Cite journal|last=Rizzi|first=Luca|last2=Dallanoce|first2=Clelia|last3=Matera|first3=Carlo|last4=Magrone|first4=Pietro|last5=Pucci|first5=Luca|last6=Gotti|first6=Cecilia|last7=Clementi|first7=Francesco|last8=De Amici|first8=Marco|date=2008-08-15|title=Epiboxidine and novel-related analogues: A convenient synthetic approach and estimation of their affinity at neuronal nicotinic acetylcholine receptor subtypes|url=http://www.sciencedirect.com/science/article/pii/S0960894X08007853|journal=Bioorganic & Medicinal Chemistry Letters|volume=18|issue=16|pages=4651–4654|doi=10.1016/j.bmcl.2008.07.016}}</ref><ref>{{Cite journal|last=Dallanoce|first=Clelia|last2=Matera|first2=Carlo|last3=Amici|first3=Marco De|last4=Rizzi|first4=Luca|last5=Pucci|first5=Luca|last6=Gotti|first6=Cecilia|last7=Clementi|first7=Francesco|last8=Micheli|first8=Carlo De|date=2012-07-01|title=The enantiomers of epiboxidine and of two related analogs: Synthesis and estimation of their binding affinity at α4β2 and α7 neuronal nicotinic acetylcholine receptors|url=http://onlinelibrary.wiley.com/doi/10.1002/chir.22052/abstract|journal=Chirality|language=en|volume=24|issue=7|pages=543–551|doi=10.1002/chir.22052|issn=1520-636X}}</ref><ref>{{Cite journal
Epiboxidine is around one-tenth as potent as epibatidine as an α4β2 agonist, but has around the same potency as an α3β4 agonist. It has only one-tenth of the analgesic power of epibatidine, but is also much less toxic.<ref>{{cite journal | vauthors = Rizzi L, Dallanoce C, Matera C, Magrone P, Pucci L, Gotti C, Clementi F, De Amici M | display-authors = 6 | title = Epiboxidine and novel-related analogues: a convenient synthetic approach and estimation of their affinity at neuronal nicotinic acetylcholine receptor subtypes | journal = Bioorganic & Medicinal Chemistry Letters | volume = 18 | issue = 16 | pages = 4651–4 | date = August 2008 | pmid = 18644719 | doi = 10.1016/j.bmcl.2008.07.016 | url = https://air.unimi.it/bitstream/2434/59291/1/Bioorganic%20%26%20Medicinal%20Chemistry%20Letters%2018%20%282008%29%204651%e2%80%934654.pdf | hdl = 2434/59291 | hdl-access = free }}</ref><ref>{{cite journal | vauthors = Dallanoce C, Matera C, De Amici M, Rizzi L, Pucci L, Gotti C, Clementi F, De Micheli C | display-authors = 6 | title = The enantiomers of epiboxidine and of two related analogs: synthesis and estimation of their binding affinity at α4β2 and α7 neuronal nicotinic acetylcholine receptors | journal = Chirality | volume = 24 | issue = 7 | pages = 543–51 | date = July 2012 | pmid = 22566097 | doi = 10.1002/chir.22052 }}</ref><ref>{{cite journal | vauthors = Badio B, Garraffo HM, Plummer CV, Padgett WL, Daly JW | title = Synthesis and nicotinic activity of epiboxidine: an isoxazole analogue of epibatidine | journal = European Journal of Pharmacology | volume = 321 | issue = 2 | pages = 189–94 | date = February 1997 | pmid = 9063687 | doi = 10.1016/S0014-2999(96)00939-9 | url = https://zenodo.org/record/1259579 }}</ref>
| pmid = 9063687
| year = 1997
| last1 = Badio | first1 = B.
| last2 = Garraffo
| last3 = Plummer
| last4 = Padgett
| last5 = Daly
| title = Synthesis and nicotinic activity of epiboxidine: an isoxazole analogue of epibatidine
| volume = 321
| issue = 2
| pages = 189–194
| journal = European Journal of Pharmacology
| doi = 10.1016/S0014-2999(96)00939-9 | first2 = H. M. | first3 = C. V. | first4 = W. L. | first5 = J. W.
}}</ref>


== Uses ==
== Uses ==


Despite its decreased potency and toxicity compared to epibatidine, epiboxidine itself is still too toxic to be developed as a drug for use in humans. It is used in scientific research<ref>{{cite journal | vauthors = Yan X, Zhao B, Butt CM, Debski EA | title = Nicotine exposure refines visual map topography through an NMDA receptor-mediated pathway | journal = The European Journal of Neuroscience | volume = 24 | issue = 11 | pages = 3026–42 | date = December 2006 | pmid = 17156364 | doi = 10.1111/j.1460-9568.2006.05204.x | s2cid = 25993659 }}</ref> and as a parent compound to derive newer analogues which may be safer and have greater potential for clinical development.<ref>{{cite journal |author-link4=Taruna Madan Gupta |vauthors=Fitch RW, Pei XF, Kaneko Y, Gupta T, Shi D, Federova I, Daly JW |date=January 2004 |title=Homoepiboxidines: further potent agonists for nicotinic receptors |journal=Bioorganic & Medicinal Chemistry |volume=12 |issue=1 |pages=179–90 |doi=10.1016/j.bmc.2003.10.015 |pmid=14697783}}</ref><ref>{{cite journal | vauthors = Cheng J, Izenwasser S, Zhang C, Zhang S, Wade D, Trudell ML | title = Synthesis and nicotinic acetylcholine receptor binding affinities of 2- and 3-isoxazolyl-8-azabicyclo[3.2.1]octanes | journal = Bioorganic & Medicinal Chemistry Letters | volume = 14 | issue = 7 | pages = 1775–8 | date = April 2004 | pmid = 15026069 | doi = 10.1016/j.bmcl.2004.01.025 }}</ref><ref>{{cite journal | vauthors = Armstrong A, Bhonoah Y, Shanahan SE | title = Aza-Prins-pinacol approach to 7-azabicyclo[2.2.1]heptanes: syntheses of (+/-)-epibatidine and (+/-)-epiboxidine | journal = The Journal of Organic Chemistry | volume = 72 | issue = 21 | pages = 8019–24 | date = October 2007 | pmid = 17867705 | doi = 10.1021/jo701536a }}</ref>
Despite its decreased potency and toxicity compared to epibatidine, epiboxidine itself is still too toxic to be developed as a drug for use in humans. It is used in scientific research<ref>{{Cite journal
| last1 = Yan | first1 = X.
| last2 = Zhao | first2 = B.
| last3 = Butt | first3 = C.
| last4 = Debski | first4 = E.
| title = Nicotine exposure refines visual map topography through an NMDA receptor-mediated pathway
| journal = The European Journal of Neuroscience
| volume = 24
| issue = 11
| pages = 3026–3042
| year = 2006
| pmid = 17156364
| doi = 10.1111/j.1460-9568.2006.05204.x
}}</ref> and as a parent compound to derive newer analogues which may be safer and have greater potential for clinical development.<ref>{{Cite journal
| pmid = 14697783
| year = 2004
| last1 = Fitch | first1 = R. W.
| last2 = Pei
| last3 = Kaneko
| last4 = Gupta
| last5 = Shi
| last6 = Federova
| last7 = Daly
| title = Homoepiboxidines: further potent agonists for nicotinic receptors
| volume = 12
| issue = 1
| pages = 179–190
| journal = Bioorganic & Medicinal Chemistry
| doi = 10.1016/j.bmc.2003.10.015 | first2 = X. F. | first3 = Y. | first4 = T. | first5 = D. | first6 = I. | first7 = J. W.
}}</ref><ref>{{Cite journal
| last1 = Cheng | first1 = J.
| last2 = Izenwasser | first2 = S.
| last3 = Zhang | first3 = C.
| last4 = Zhang | first4 = S.
| last5 = Wade | first5 = D.
| last6 = Trudell | first6 = M.
| title = Synthesis and nicotinic acetylcholine receptor binding affinities of 2- and 3-isoxazolyl-8-azabicyclo3.2.1octanes
| journal = Bioorganic & Medicinal Chemistry Letters
| volume = 14
| issue = 7
| pages = 1775–1778
| year = 2004
| pmid = 15026069
| doi = 10.1016/j.bmcl.2004.01.025
}}</ref><ref>{{Cite journal
| last1 = Armstrong | first1 = A.
| last2 = Bhonoah | first2 = Y.
| last3 = Shanahan | first3 = S.
| title = Aza-Prins-pinacol approach to 7-azabicyclo2.2.1heptanes: syntheses of (+/-)-epibatidine and (+/-)-epiboxidine
| journal = The Journal of Organic Chemistry
| volume = 72
| issue = 21
| pages = 8019–8024
| year = 2007
| pmid = 17867705
| doi = 10.1021/jo701536a
}}</ref>


==See also==
== See also ==
* [[ABT-418]]
* [[ABT-418]]


==References==
== References ==
{{Reflist|2}}
{{Reflist|2}}


Latest revision as of 10:23, 20 November 2022

Epiboxidine
Legal status
Legal status
  • Investigational
Identifiers
  • (1R,4S,6S)-6-(3-Methylisoxazol-5-yl)-7-azabicyclo[2.2.1]heptane
CAS Number
PubChem CID
ChemSpider
UNII
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC10H14N2O
Molar mass178.235 g·mol−1
3D model (JSmol)
  • CC1=NOC(=C1)[C@H]2C[C@@H]3CC[C@H]2N3
  • InChI=1S/C10H14N2O/c1-6-4-10(13-12-6)8-5-7-2-3-9(8)11-7/h4,7-9,11H,2-3,5H2,1H3/t7-,8-,9+/m0/s1
  • Key:GEEFPQBPVBFCSD-XHNCKOQMSA-N

Epiboxidine is a chemical compound which acts as a partial agonist at neural nicotinic acetylcholine receptors, binding to both the α3β4 and the α4β2 subtypes. It was developed as a less toxic analogue of the potent frog-derived alkaloid epibatidine, which is around 200 times stronger than morphine as an analgesic but produces extremely dangerous toxic nicotinic side effects.

Epiboxidine is around one-tenth as potent as epibatidine as an α4β2 agonist, but has around the same potency as an α3β4 agonist. It has only one-tenth of the analgesic power of epibatidine, but is also much less toxic.[1][2][3]

Uses

[edit]

Despite its decreased potency and toxicity compared to epibatidine, epiboxidine itself is still too toxic to be developed as a drug for use in humans. It is used in scientific research[4] and as a parent compound to derive newer analogues which may be safer and have greater potential for clinical development.[5][6][7]

See also

[edit]

References

[edit]
  1. ^ Rizzi L, Dallanoce C, Matera C, Magrone P, Pucci L, Gotti C, et al. (August 2008). "Epiboxidine and novel-related analogues: a convenient synthetic approach and estimation of their affinity at neuronal nicotinic acetylcholine receptor subtypes" (PDF). Bioorganic & Medicinal Chemistry Letters. 18 (16): 4651–4. doi:10.1016/j.bmcl.2008.07.016. hdl:2434/59291. PMID 18644719.
  2. ^ Dallanoce C, Matera C, De Amici M, Rizzi L, Pucci L, Gotti C, et al. (July 2012). "The enantiomers of epiboxidine and of two related analogs: synthesis and estimation of their binding affinity at α4β2 and α7 neuronal nicotinic acetylcholine receptors". Chirality. 24 (7): 543–51. doi:10.1002/chir.22052. PMID 22566097.
  3. ^ Badio B, Garraffo HM, Plummer CV, Padgett WL, Daly JW (February 1997). "Synthesis and nicotinic activity of epiboxidine: an isoxazole analogue of epibatidine". European Journal of Pharmacology. 321 (2): 189–94. doi:10.1016/S0014-2999(96)00939-9. PMID 9063687.
  4. ^ Yan X, Zhao B, Butt CM, Debski EA (December 2006). "Nicotine exposure refines visual map topography through an NMDA receptor-mediated pathway". The European Journal of Neuroscience. 24 (11): 3026–42. doi:10.1111/j.1460-9568.2006.05204.x. PMID 17156364. S2CID 25993659.
  5. ^ Fitch RW, Pei XF, Kaneko Y, Gupta T, Shi D, Federova I, Daly JW (January 2004). "Homoepiboxidines: further potent agonists for nicotinic receptors". Bioorganic & Medicinal Chemistry. 12 (1): 179–90. doi:10.1016/j.bmc.2003.10.015. PMID 14697783.
  6. ^ Cheng J, Izenwasser S, Zhang C, Zhang S, Wade D, Trudell ML (April 2004). "Synthesis and nicotinic acetylcholine receptor binding affinities of 2- and 3-isoxazolyl-8-azabicyclo[3.2.1]octanes". Bioorganic & Medicinal Chemistry Letters. 14 (7): 1775–8. doi:10.1016/j.bmcl.2004.01.025. PMID 15026069.
  7. ^ Armstrong A, Bhonoah Y, Shanahan SE (October 2007). "Aza-Prins-pinacol approach to 7-azabicyclo[2.2.1]heptanes: syntheses of (+/-)-epibatidine and (+/-)-epiboxidine". The Journal of Organic Chemistry. 72 (21): 8019–24. doi:10.1021/jo701536a. PMID 17867705.
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