title: Synthesis and activity of substituted carbamates as potentiators of the alpha4beta2 nicotinic acetylcholine receptor.
abstract: The synthesis and structure-activity relationship of a series of carbamate potentiators of alpha4beta2 nAChR is reported herein. These compounds were highly selective for alpha4beta2 over other nAChR subtypes. In addition, compounds increased the response of alpha4beta2 nAChRs to acetylcholine, as measured with patch-clamp electrophysiology.
authors.affiliation: Department of Medicinal Chemistry, Amgen Inc., 1 Kendall Square, Building 1000, Cambridge, MA, USA. stephanie.springer@amgen.com
authors.forename: Stephanie K
authors.initials: SK
authors.lastname: Springer
authors.forename: Katrina S
authors.initials: KS
authors.lastname: Woodin
authors.forename: Virginia
authors.initials: V
authors.lastname: Berry
authors.forename: Alessandro A
authors.initials: AA
authors.lastname: Boezio
authors.forename: Lei
authors.initials: L
authors.lastname: Cao
authors.forename: Kristie
authors.initials: K
authors.lastname: Clarkin
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Harmange
authors.forename: Markus
authors.initials: M
authors.lastname: Hierl
authors.forename: Johannes
authors.initials: J
authors.lastname: Knop
authors.forename: Annika B
authors.initials: AB
authors.lastname: Malmberg
authors.forename: Jeff S
authors.initials: JS
authors.lastname: McDermott
authors.forename: Hung Q
authors.initials: HQ
authors.lastname: Nguyen
authors.forename: Daniel
authors.initials: D
authors.lastname: Waldon
authors.forename: Brian K
authors.initials: BK
authors.lastname: Albrecht
authors.forename: Stefan I
authors.initials: SI
authors.lastname: McDonough
mesh_terms: D000109:Acetylcholine / Q000737:chemistry; D002118:Calcium / Q000737:chemistry; D002219:Carbamates / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D006801:Humans; D008956:Models, Chemical; D009420:Nervous System / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011720:Pyrazoles / Q000737:chemistry; D011725:Pyridines / Q000737:chemistry; D011978:Receptors, Nicotinic / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D002219:Carbamates; D011720:Pyrazoles; D011725:Pyridines; D011978:Receptors, Nicotinic; C403531:nicotinic receptor alpha4beta2; D000109:Acetylcholine; D002118:Calcium