Syntheses and anticholinesterase activity of tetrahydrobenzazepine carbamates

J Med Chem. 1994 Jun 24;37(13):1996-2000. doi: 10.1021/jm00039a013.

Abstract

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.

MeSH terms

  • Administration, Oral
  • Amnesia / drug therapy
  • Animals
  • Avoidance Learning / drug effects
  • Benzazepines / chemical synthesis*
  • Benzazepines / pharmacology
  • Carbamates / chemical synthesis*
  • Carbamates / pharmacology
  • Carbamates / therapeutic use
  • Cholinesterase Inhibitors / administration & dosage
  • Cholinesterase Inhibitors / chemical synthesis*
  • Cholinesterase Inhibitors / pharmacology
  • Cholinesterase Inhibitors / therapeutic use
  • Cholinesterases / metabolism
  • Dose-Response Relationship, Drug
  • Injections, Intraperitoneal
  • Magnetic Resonance Spectroscopy
  • Male
  • Mice

Substances

  • Benzazepines
  • Carbamates
  • Cholinesterase Inhibitors
  • 1,5-methano-2-methyl-2,3,4,5-tetrahydro-1H-2-benzazepin-7-yl n-hexylcarbamate
  • Cholinesterases