In pursuit of alpha4beta2 nicotinic receptor partial agonists for smoking cessation: carbon analogs of (-)-cytisine

Bioorg Med Chem Lett. 2005 Jun 15;15(12):2974-9. doi: 10.1016/j.bmcl.2005.04.036.

Abstract

The preparation and biological activity of analogs of (-)-cytisine, an alpha4beta2 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.

MeSH terms

  • Alkaloids / chemistry
  • Alkaloids / pharmacology*
  • Animals
  • Azocines / chemistry
  • Azocines / pharmacology
  • Carbon / chemistry*
  • Dopamine / metabolism*
  • Nicotinic Agonists / chemistry
  • Nicotinic Agonists / pharmacology*
  • Nucleus Accumbens / drug effects*
  • Quinolizines / chemistry
  • Quinolizines / pharmacology
  • Rats
  • Receptors, Nicotinic / chemistry*
  • Receptors, Nicotinic / metabolism
  • Smoking Cessation
  • Structure-Activity Relationship

Substances

  • Alkaloids
  • Azocines
  • Nicotinic Agonists
  • Quinolizines
  • Receptors, Nicotinic
  • nicotinic receptor alpha4beta2
  • cytisine
  • Carbon
  • Dopamine