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

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.

• Authors: Carlo Mustazza, Anna Borioni, Maria Rosaria Del Giudice, Franco Gatta, Rosella Ferretti, Annarita Meneguz, Maria Teresa Volpe, Paola Lorenzini
• Journal: European journal of medicinal chemistry (Eur J Med Chem) Vol. 37 Issue 2 Pg. 91-109 (Feb 2002) ISSN: 0223-5234 [Print] France
• PMID: 11858843 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Carbamates
• Cholinesterase Inhibitors
• Phenylcarbamates
• Acetylcholinesterase
• Rivastigmine

Topics

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