Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1371511 | Bioorganic & Medicinal Chemistry Letters | 2012 | 4 Pages |
Abstract
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 (Ki <35 nM) at the human α4β2 nAChR subtype, and very low affinity for the human α7, α3β4 (ganglion) and α1β1γδ (muscle) subtypes (Ki >500 nM).
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Related Topics
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Organic Chemistry
Authors
Jon-Paul Strachan, Jarrett J. Farias, Jenny Zhang, William S. Caldwell, Balwinder S. Bhatti,