Syntheses and anticholinesterase activity of tetrahydrobenzazepine carbamates.
The synthesis of a series of alkylcarbamates of 1,5-methano-2,3,4,5-tetrahydro-1H-2-benzazepin-7-ol is reported. Many of these compounds are potent acetylcholinesterase (AChE) inhibitors. The in vitro AChE inhibition, cholinergic effects, acute toxicity, and elevation of brain acetylcholine levels in vivo of this series of compounds are described. A representative compound, 1d (5.6 mg/kg, po), was able to reverse hemicolinium-3-induced amnesia in the mouse passive avoidance assay.
Department of Medicinal Chemistry, Pfizer Inc., Groton, Connecticut 06340.
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YL
Chen
D
D
Liston
J
J
Nielsen
D
D
Chapin
A
A
Dunaiskis
K
K
Hedberg
J
J
Ives
J
J
Johnson
S
S
Jones
D000284:Administration, Oral; D000647:Amnesia / Q000188:drug therapy; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001552:Benzazepines / Q000138:chemical synthesis* / Q000494:pharmacology; D002219:Carbamates / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D002802:Cholinesterases / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007274:Injections, Intraperitoneal; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice
D001552:Benzazepines; D002219:Carbamates; D002800:Cholinesterase Inhibitors; C088276:1,5-methano-2-methyl-2,3,4,5-tetrahydro-1H-2-benzazepin-7-yl n-hexylcarbamate; D002802:Cholinesterases