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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Veröffentlicht in:	Bioorganic & medicinal chemistry letters 2012-08, Vol.22 (15), p.5089-5092
Hauptverfasser:	Strachan, Jon-Paul, Farias, Jarrett J., Zhang, Jenny, Caldwell, William S., Bhatti, Balwinder S.
Format:	Artikel
Sprache:	eng
Schlagworte:	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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Zusammenfassung:	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