3,5-Bicyclic aryl piperidines: a novel class of alpha4beta2 neuronal nicotinic receptor partial agonists for smoking cessation

Bioorg Med Chem Lett. 2005 Nov 15;15(22):4889-97. doi: 10.1016/j.bmcl.2005.08.035.


3,5-Bicyclic aryl piperidines are a new class of high-affinity alpha4beta2 nicotinic receptor agents. We have sought nicotinic receptor partial agonists of the alpha4beta2 nicotinic acetylcholine receptor for smoking cessation, and a number of compounds fulfill potency, selectivity, and efficacy requirements in vitro. In vivo, selected agents demonstrate potent partial agonist efficacy on the mesolimbic dopamine system, a key measure of therapeutic potential for smoking cessation.

MeSH terms

  • Animals
  • Cyclization
  • Molecular Structure
  • Piperidines / chemistry*
  • Piperidines / classification
  • Piperidines / pharmacology*
  • Rats
  • Receptors, Nicotinic / metabolism*
  • Smoking Cessation / methods*
  • Structure-Activity Relationship


  • Piperidines
  • Receptors, Nicotinic
  • nicotinic receptor alpha4beta2