Diazaspirocyclic compounds as selective ligands for the α4β2 nicotinic acetylcholine receptor

Diazaspirocyclic ligands have been synthesized in four steps as selective α4β2 nicotinic acetylcholine receptor antagonists. Structural assignment of 1-(pyridin-3-yl)-2-spiropyrrolidino-3,2′-1-azabiclo[2.2.1]heptane 2, was confirmed using a combination of NMR experiments on a key intermediate, spiro...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2012-08, Vol.22 (15), p.5089-5092
Main Authors: Strachan, Jon-Paul, Farias, Jarrett J., Zhang, Jenny, Caldwell, William S., Bhatti, Balwinder S.
Format: Article
Language:English
Subjects:
acetylcholine
antagonists
Aza Compounds - chemistry
Biological and medical sciences
chemistry
Diazaspirocyclic
ganglia
heptane
Heptanes - chemistry
Humans
Ligands
Magnetic Resonance Spectroscopy
Medical sciences
muscles
Nicotinic
Nicotinic Antagonists - chemical synthesis
Nicotinic Antagonists - chemistry
Nicotinic Antagonists - metabolism
nuclear magnetic resonance spectroscopy
Pharmacology. Drug treatments
Protein Binding
Protein Isoforms - antagonists & inhibitors
Protein Isoforms - metabolism
Receptors, Nicotinic - chemistry
Receptors, Nicotinic - metabolism
Spiro Compounds - chemical synthesis
Spiro Compounds - chemistry
Spiro Compounds - metabolism
α4β2
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Summary:Diazaspirocyclic ligands have been synthesized in four steps as selective α4β2 nicotinic acetylcholine receptor antagonists. Structural assignment of 1-(pyridin-3-yl)-2-spiropyrrolidino-3,2′-1-azabiclo[2.2.1]heptane 2, was confirmed using a combination of NMR experiments on a key intermediate, spirolactam 9. All three target compounds synthesized in this diazaspirocyclic series exhibited high affinity (Ki500nM).
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2012.05.108