Synthesis and cholinesterase activity of phenylcarbamates related to Rivastigmine, a therapeutic agent for Alzheimer's disease.
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.
Mustazza
Carlo
C
Laboratorio di Chimica del Farmaco, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy. mustazza@iss.it
Borioni
Anna
A
Del Giudice
Maria Rosaria
MR
Gatta
Franco
F
Ferretti
Rosella
R
Meneguz
Annarita
A
Volpe
Maria Teresa
MT
Lorenzini
Paola
P
D000110:Acetylcholinesterase / Q000097:blood / Q000378:metabolism; D000284:Administration, Oral; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000503:physiopathology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000502:physiology; D002219:Carbamates / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical; D020128:Inhibitory Concentration 50; D051379:Mice; D048448:Phenylcarbamates; D051381:Rats; D000068836:Rivastigmine; D013329:Structure-Activity Relationship
D002219:Carbamates; D002800:Cholinesterase Inhibitors; D048448:Phenylcarbamates; D000110:Acetylcholinesterase; D000068836:Rivastigmine