title: Synthesis and SAR studies of 1,4-diazabicyclo[3.2.2]nonane phenyl carbamates--subtype selective, high affinity alpha7 nicotinic acetylcholine receptor agonists.
abstract: The synthesis and SAR studies about the bicyclic amine, carbamate linker and aromatic ring of a 1,4-diazabicyclo[3.2.2]nonane phenyl carbamate series of alpha7 nAChR agonists is described. The development of the medicinal chemistry strategy and SAR which led to the identification of 5 and 7aa as subtype selective, high affinity alpha7 agonists as excellent leads for further evaluation is discussed, along with key physicochemical and pharmacokinetic data highlighting their lead potential.
authors: Neuroscience Medicinal Chemistry, Pfizer Global Research & Development, Groton, CT 06340, United States. christopher.j.odonnell@pfizer.com
authors: Christopher J
authors: CJ
authors: O'Donnell
authors: Langu
authors: L
authors: Peng
authors: Brian T
authors: BT
authors: O'Neill
authors: Eric P
authors: EP
authors: Arnold
authors: Robert J
authors: RJ
authors: Mather
authors: Steven B
authors: SB
authors: Sands
authors: Alka
authors: A
authors: Shrikhande
authors: Lorraine A
authors: LA
authors: Lebel
authors: Douglas K
authors: DK
authors: Spracklin
authors: Frank M
authors: FM
authors: Nedza
mesh_terms: D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D002219:Carbamates / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D002460:Cell Line; D006801:Humans; D008297:Male; D018722:Nicotinic Agonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D048448:Phenylcarbamates / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: C543968:1,4-diazabicyclo(3.2.2)nonane phenyl carbamate; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002219:Carbamates; C579167:Chrna7 protein, human; C579165:Chrna7 protein, rat; D018722:Nicotinic Agonists; D048448:Phenylcarbamates; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor