title: 3,5-Bicyclic aryl piperidines: a novel class of alpha4beta2 neuronal nicotinic receptor partial agonists for smoking cessation.
abstract: 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.
authors.affiliation: Pfizer Global Research and Development, Groton Laboratories, Eastern Point Road, Groton, CT 06340, USA. jwcoe@pfizer.com
authors.forename: Jotham W
authors.initials: JW
authors.lastname: Coe
authors.forename: Paige R
authors.initials: PR
authors.lastname: Brooks
authors.forename: Michael C
authors.initials: MC
authors.lastname: Wirtz
authors.forename: Crystal G
authors.initials: CG
authors.lastname: Bashore
authors.forename: Krista E
authors.initials: KE
authors.lastname: Bianco
authors.forename: Michael G
authors.initials: MG
authors.lastname: Vetelino
authors.forename: Eric P
authors.initials: EP
authors.lastname: Arnold
authors.forename: Lorraine A
authors.initials: LA
authors.lastname: Lebel
authors.forename: Carol B
authors.initials: CB
authors.lastname: Fox
authors.forename: F David
authors.initials: FD
authors.lastname: Tingley
authors.forename: David W
authors.initials: DW
authors.lastname: Schulz
authors.forename: Thomas I
authors.initials: TI
authors.lastname: Davis
authors.forename: Steven B
authors.initials: SB
authors.lastname: Sands
authors.forename: Robert S
authors.initials: RS
authors.lastname: Mansbach
authors.forename: Hans
authors.initials: H
authors.lastname: Rollema
authors.forename: Brian T
authors.initials: BT
authors.lastname: O'Neill
mesh_terms: D000818:Animals; D003500:Cyclization; D015394:Molecular Structure; D010880:Piperidines / Q000737:chemistry* / Q000145:classification / Q000494:pharmacology*; D051381:Rats; D011978:Receptors, Nicotinic / Q000378:metabolism*; D016540:Smoking Cessation / Q000379:methods*; D013329:Structure-Activity Relationship
chemical_list: D010880:Piperidines; D011978:Receptors, Nicotinic; C403531:nicotinic receptor alpha4beta2