title: A novel series of [3.2.1] azabicyclic biaryl ethers as alpha3beta4 and alpha6/4beta4 nicotinic receptor agonists.
abstract: We report the synthesis of a series of [3.2.1]azabicyclic biaryl ethers as selective agonists of alpha3- and alpha6-containing nicotinic receptors. In particular, compound 17a from this series is a potent alpha3beta4 and alpha6/4beta4 receptor agonist in terms of both binding and functional activity. Compound 17a also shows potent in vivo activity in CNS-mediated animal models that are sensitive to antipsychotic drugs. Compound 17a may thus be a useful tool for studying the role of alpha3beta4 and alpha6/4beta4 nicotinic receptors in CNS pharmacology.
authors.affiliation: Pfizer Global Research & Development, Eastern Point Road, Groton, CT 06340, United States. jal3rd@gmail.com
authors.forename: John A
authors.initials: JA
authors.lastname: Lowe
authors.forename: Shari L
authors.initials: SL
authors.lastname: DeNinno
authors.forename: Jotham W
authors.initials: JW
authors.lastname: Coe
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Scot
authors.initials: S
authors.lastname: Mente
authors.forename: Raymond S
authors.initials: RS
authors.lastname: Hurst
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Mather
authors.forename: Karen M
authors.initials: KM
authors.lastname: Ward
authors.forename: Alka
authors.initials: A
authors.lastname: Shrikhande
authors.forename: Hans
authors.initials: H
authors.lastname: Rollema
authors.forename: David E
authors.initials: DE
authors.lastname: Johnson
authors.forename: Weldon
authors.initials: W
authors.lastname: Horner
authors.forename: Roxanne
authors.initials: R
authors.lastname: Gorczyca
authors.forename: F David
authors.initials: FD
authors.lastname: Tingley
authors.forename: Rouba
authors.initials: R
authors.lastname: Kozak
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Majchrzak
authors.forename: Theresa
authors.initials: T
authors.lastname: Tritto
authors.forename: Jen
authors.initials: J
authors.lastname: Sadlier
authors.forename: Chris L
authors.initials: CL
authors.lastname: Shaffer
authors.forename: Brenda
authors.initials: B
authors.lastname: Ellerbrock
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Osgood
authors.forename: Mary C
authors.initials: MC
authors.lastname: MacDougall
authors.forename: Laura L
authors.initials: LL
authors.lastname: McDowell
mesh_terms: D053961:Azabicyclo Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D053961:Azabicyclo Compounds; D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D013449:Sulfonamides; C427403:alpha(4)beta(4) nicotinic receptor; C403530:nicotinic receptor alpha3beta4; C104518:nicotinic receptor alpha6