Synthesis and cholinesterase activity of phenylcarbamates related to Rivastigmine, a therapeutic agent for Alzheimer's disease

Eur J Med Chem. 2002 Feb;37(2):91-109. doi: 10.1016/s0223-5234(01)01324-1.

Abstract

In order to develop new cholinesterase agents effective against Alzheimer's disease (AD) we synthesized some phenylcarbamates structurally related to Rivastigmine and evaluated their in vitro and in vivo biological activity. Among the compounds which displayed the most significant in vitro activity, 1-[1-(3-dimethylcarbamoyloxyphenyl)ethyl]piperidine (31b), in addition to a simple and cheaper synthesis, showed lower toxicity and very similar therapeutic index in comparison with Rivastigmine.

Publication types

  • Comparative Study

MeSH terms

  • Acetylcholinesterase / blood
  • Acetylcholinesterase / metabolism
  • Administration, Oral
  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / physiopathology
  • Animals
  • Brain / drug effects
  • Brain / physiology
  • Carbamates / chemical synthesis*
  • Carbamates / chemistry*
  • Carbamates / pharmacology*
  • Carbamates / therapeutic use
  • Cholinesterase Inhibitors / chemical synthesis*
  • Cholinesterase Inhibitors / chemistry
  • Cholinesterase Inhibitors / pharmacology*
  • Cholinesterase Inhibitors / therapeutic use
  • Drug Evaluation, Preclinical
  • Inhibitory Concentration 50
  • Mice
  • Phenylcarbamates*
  • Rats
  • Rivastigmine
  • Structure-Activity Relationship

Substances

  • Carbamates
  • Cholinesterase Inhibitors
  • Phenylcarbamates
  • Acetylcholinesterase
  • Rivastigmine