Synthesis and preliminary in vivo evaluation of new 2-Aryl-6-methyl-1,2-dihydro-1H-pyridin-4-ones and 2-Aryl-6-methylpiperidin-4-ols, as potential anti-amnesiant agents.
A revisited synthesis of 2-aryl-6-methyl-1,2-dihydro-1H-pyridin-4-ones and their saturated analogues 2-aryl-6-methylpiperidin-4-ols is described. A five steps procedure, using the sulfinimine chemistry, to prepare a key intermediate beta-(6-chloronicotinic)-beta-amino ester is also reported. In vivo spontaneous working memory activity of these compounds has been investigated in the mouse. Results obtained with 2-(3-chlorophenyl)-6-methyl-1,2-dihydro-1H-pyridin-4-one 9b, the most effective derivative in this model, have been reported.
Leflemme
Nicolas
N
Centre d'Etudes et de Recherche sur le Médicament de Normandie, 1 rue Vaubénard 14032, Caen Cedex, France.
Freret
Thomas
T
Boulouard
Michel
M
Dallemagne
Patrick
P
Rault
Sylvain
S
D000647:Amnesia / Q000517:prevention & control*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects; D051379:Mice; D015394:Molecular Structure; D010880:Piperidines / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology*; D011728:Pyridones / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology*; D012601:Scopolamine / Q000494:pharmacology; D013237:Stereoisomerism
D010880:Piperidines; D011728:Pyridones; D012601:Scopolamine