title: Identification and SAR around N-{2-[4-(2,3-dihydro-benzo[1,4]dioxin-2-ylmethyl)-[1,4]diazepan-1-yl]-ethyl}-2-phenoxy-nicotinamide, a selective alpha2C adrenergic receptor antagonist.
abstract: The discovery of the CNS-penetrant and selective alpha(2C) adrenergic receptor antagonist N-{2-[4-(2,3-dihydro-benzo[1,4]dioxin-2-ylmethyl)-[1,4]diazepan-1-yl]-ethyl}-2-phenoxy-nicotinamide, 13 is described. Structure-activity studies demonstrate the structural requirements for binding affinity, functional activity, and selectivity over other alpha(2)-AR subtypes.
authors.affiliation: Pfizer Global Research and Development, Cambridge Laboratories, Cambridge, MA 02139, USA.
authors.forename: Snahel D
authors.initials: SD
authors.lastname: Patel
authors.forename: Wendy M
authors.initials: WM
authors.lastname: Habeski
authors.forename: Hyunsuk
authors.initials: H
authors.lastname: Min
authors.forename: Jiansu
authors.initials: J
authors.lastname: Zhang
authors.forename: Robin
authors.initials: R
authors.lastname: Roof
authors.forename: Bradley
authors.initials: B
authors.lastname: Snyder
authors.forename: Gary
authors.initials: G
authors.lastname: Bora
authors.forename: Brian
authors.initials: B
authors.lastname: Campbell
authors.forename: Cheryl
authors.initials: C
authors.lastname: Li
authors.forename: Debra
authors.initials: D
authors.lastname: Hidayetoglu
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Johnson
authors.forename: Archana
authors.initials: A
authors.lastname: Chaudhry
authors.forename: Maura E
authors.initials: ME
authors.lastname: Charlton
authors.forename: Natasha M
authors.initials: NM
authors.lastname: Kablaoui
mesh_terms: D058669:Adrenergic alpha-2 Receptor Antagonists; D000818:Animals; D001381:Azepines / Q000138:chemical synthesis* / Q000494:pharmacology; D001921:Brain / Q000378:metabolism; D002490:Central Nervous System / Q000187:drug effects; D002555:Cerebrospinal Fluid / Q000378:metabolism; D002626:Chemistry, Pharmaceutical / Q000379:methods; D015195:Drug Design; D006801:Humans; D007700:Kinetics; D008297:Male; D008968:Molecular Conformation; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D011921:Rats, Inbred WKY; D018341:Receptors, Adrenergic, alpha-2 / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D058669:Adrenergic alpha-2 Receptor Antagonists; D001381:Azepines; C540069:N-(2-(4-(2,3-dihydrobenzo(1,4)dioxin-2-ylmethyl)-(1,4)diazepan-2-yl)ethyl)-2-phenoxynicotinamide; D018341:Receptors, Adrenergic, alpha-2; D009536:Niacinamide