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.
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.
Patel
Snahel D
SD
Pfizer Global Research and Development, Cambridge Laboratories, Cambridge, MA 02139, USA.
Habeski
Wendy M
WM
Min
Hyunsuk
H
Zhang
Jiansu
J
Roof
Robin
R
Snyder
Bradley
B
Bora
Gary
G
Campbell
Brian
B
Li
Cheryl
C
Hidayetoglu
Debra
D
Johnson
Douglas S
DS
Chaudhry
Archana
A
Charlton
Maura E
ME
Kablaoui
Natasha M
NM
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
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