title: In pursuit of alpha4beta2 nicotinic receptor partial agonists for smoking cessation: carbon analogs of (-)-cytisine.
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.
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: Michael G
authors.initials: MG
authors.lastname: Vetelino
authors.forename: Crystal G
authors.initials: CG
authors.lastname: Bashore
authors.forename: Michael C
authors.initials: MC
authors.lastname: Wirtz
authors.forename: Paige R
authors.initials: PR
authors.lastname: Brooks
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: Steven B
authors.initials: SB
authors.lastname: Sands
authors.forename: Thomas I
authors.initials: TI
authors.lastname: Davis
authors.forename: David W
authors.initials: DW
authors.lastname: Schulz
authors.forename: Hans
authors.initials: H
authors.lastname: Rollema
authors.forename: F David
authors.initials: FD
authors.lastname: Tingley
authors.forename: Brian T
authors.initials: BT
authors.lastname: O'Neill
mesh_terms: D000470:Alkaloids / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D001392:Azocines / Q000737:chemistry / Q000494:pharmacology; D002244:Carbon / Q000737:chemistry*; D004298:Dopamine / Q000378:metabolism*; D018722:Nicotinic Agonists / Q000737:chemistry / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000187:drug effects*; D011807:Quinolizines / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D011978:Receptors, Nicotinic / Q000737:chemistry* / Q000378:metabolism; D016540:Smoking Cessation; D013329:Structure-Activity Relationship; D000093843:Quinolizidine Alkaloids
chemical_list: D000470:Alkaloids; D001392:Azocines; D002244:Carbon; D004298:Dopamine; D018722:Nicotinic Agonists; D011807:Quinolizines; D011978:Receptors, Nicotinic; C403531:nicotinic receptor alpha4beta2; C004712:cytisine; D000093843:Quinolizidine Alkaloids