title: Synthesis and biological evaluation of new donepezil-like Thiaindanones as AChE inhibitors.
abstract: 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).
authors.affiliation: Centre d'Etudes et de Recherche sur le Médicament de Normandie, UFR des Sciences Pharmaceutiques, Université de Caen Basse Normandie, Caen cedex, France.
authors.forename: Ziad
authors.initials: Z
authors.lastname: Omran
authors.forename: Silvia
authors.initials: S
authors.lastname: Stiebing
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Godard
authors.forename: Jana
authors.initials: J
authors.lastname: Sopkova-De Oliveira-Santos
authors.forename: Patrick
authors.initials: P
authors.lastname: Dallemagne
mesh_terms: 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
chemical_list: D000081:Acetamides; D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D000077265:Donepezil