title: 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.affiliation: Laboratorio di Chimica del Farmaco, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy. mustazza@iss.it
authors.forename: Carlo
authors.initials: C
authors.lastname: Mustazza
authors.forename: Anna
authors.initials: A
authors.lastname: Borioni
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Del Giudice
authors.forename: Franco
authors.initials: F
authors.lastname: Gatta
authors.forename: Rosella
authors.initials: R
authors.lastname: Ferretti
authors.forename: Annarita
authors.initials: A
authors.lastname: Meneguz
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Volpe
authors.forename: Paola
authors.initials: P
authors.lastname: Lorenzini
mesh_terms: 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
chemical_list: D002219:Carbamates; D002800:Cholinesterase Inhibitors; D048448:Phenylcarbamates; D000110:Acetylcholinesterase; D000068836:Rivastigmine