Synthesis and biological evaluation as AChE inhibitors of new indanones and thiaindanones related to donepezil.
Sixty-four new indanones and thiaindanones related to donepezil were synthesized and evaluated in vitro as potential AChE inhibitors. Among them, 11 derivatives were found to inhibit the enzyme in the submicromolar range; the best compound revealed its inhibitory activity with an IC50 in the same range (0.06 microM) than the reference compound, donepezil (IC50=0.02 microM).
Omran
Ziad
Z
Centre d'études et de recherche sur le médicament de Normandie, département de pharmacochimie U.F.R. des sciences pharmaceutiques, université de Caen Basse-Normandie, boulevard Becquerel, 14032 Caen cedex, France.
Cailly
Thomas
T
Lescot
Elodie
E
Santos
Jana Sopkova-de Oliveira
JS
Agondanou
Jean-Hugues
JH
Lisowski
Vincent
V
Fabis
Frédéric
F
Godard
Anne-Marie
AM
Stiebing
Silvia
S
Le Flem
Guillaume
G
Boulouard
Michel
M
Dauphin
François
F
Dallemagne
Patrick
P
Rault
Sylvain
S
D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D000077265:Donepezil; D015195:Drug Design; D007189:Indans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D000077265:Donepezil