Synthesis and nicotinic acetylcholine receptor binding affinities of 2- and 3-isoxazolyl-8-azabicyclo[3.2.1]octanes

Jie Cheng, Sari E Izenwasser, Chunming Zhang, Suhong Zhang, Dean Wade, Mark L. Trudell

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

A series of epiboxidine homologues, 2- and 3-isoxazole substituted 8-azabicyclo[3.2.1]octane derivatives was synthesized and evaluated as potential ligands for neuronal nicotinic acetylcholine receptors in [ 3H]cytisine labeled rat brain. The 2β-isoxazolyl-8-azabicyclo[3. 2.1]octane 9b (Ki=3 nM) was the most potent compound of the series with a binding affinity twice that of nicotine. The 3β-isoxazolyl-8- azabicyclo[3.2.1]octane 15b (Ki=148 nM) exhibited moderate affinity while the corresponding 2α- and 3α-isomers exhibited micromolar binding affinity.

Original languageEnglish
Pages (from-to)1775-1778
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume14
Issue number7
DOIs
StatePublished - Apr 1 2004

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Nicotinic Receptors
Isoxazoles
Nicotine
Isomers
Rats
Brain
Ligands
Derivatives
8-azabicyclo(3.2.1)octane
epiboxidine
cytisine
octane

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science

Cite this

Synthesis and nicotinic acetylcholine receptor binding affinities of 2- and 3-isoxazolyl-8-azabicyclo[3.2.1]octanes. / Cheng, Jie; Izenwasser, Sari E; Zhang, Chunming; Zhang, Suhong; Wade, Dean; Trudell, Mark L.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 14, No. 7, 01.04.2004, p. 1775-1778.

Research output: Contribution to journalArticle

Cheng, Jie ; Izenwasser, Sari E ; Zhang, Chunming ; Zhang, Suhong ; Wade, Dean ; Trudell, Mark L. / Synthesis and nicotinic acetylcholine receptor binding affinities of 2- and 3-isoxazolyl-8-azabicyclo[3.2.1]octanes. In: Bioorganic and Medicinal Chemistry Letters. 2004 ; Vol. 14, No. 7. pp. 1775-1778.
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