In pursuit of α4β2 nicotinic receptor partial agonists for smoking cessation: Carbon analogs of (−)-cytisine

The preparation and biological activity of analogs of (−)-cytisine, an α4β2 nicotinic receptor partial agonist, are discussed. All-carbon-containing phenyl ring replacements of the pyridone ring system, generated via Heck cyclization protocols, exhibited weaker affinity and lower efficacy partial agonist profiles relative to (−)-cytisine. In vivo, selected compounds exhibit lower efficacy partial agonist profiles than that of (−)-cytisine.

Figure optionsDownload as PowerPoint slide