Synthesis and biological evaluation of new donepezil-like Thiaindanones as AChE inhibitors.
Pharmacomodulations of previously reported thiaindanones related to donepezil were achieved with the aim to enhance their AChE inhibitory activity. Condensation of the cyclopentane carbonyl group into hydrazone or cyanolefine derivatives, as well as its hydrogenation and the subsequent substitution of the resulting hydroxyl group led to new 2-(4-benzylpiperazin-1-yl)-N-(1,3-dibromo-6-hydroxy-5,6-dihydro-4H-cyclopenta[c]thien-4-yl) acetamides. The in vitro evaluation of this new series, according to the method of Ellman, shows however that it conserved only partially the biological activity. The best compound remains the alcohol 11 (IC(50) = 0.40 microM, against 0.02 microM for donepezil).
Omran
Ziad
Z
Centre d'Etudes et de Recherche sur le Médicament de Normandie, UFR des Sciences Pharmaceutiques, Université de Caen Basse Normandie, Caen cedex, France.
Stiebing
Silvia
S
Godard
Anne-Marie
AM
Sopkova-De Oliveira-Santos
Jana
J
Dallemagne
Patrick
P
D000081:Acetamides / Q000138:chemical synthesis / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D000077265:Donepezil; D006801:Humans; D007189:Indans / Q000138:chemical synthesis* / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D010880:Piperidines; D013329:Structure-Activity Relationship
D000081:Acetamides; D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D000077265:Donepezil