Tacrine derivatives as inhibitors of acetylcholinesterase

C - Chemistry – Metallurgy – 07 – D

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C07D 401/12 (2006.01) A61K 31/473 (2006.01) A61P 25/28 (2006.01)

Patent

CA 2530780

The invention provides compounds of formula: (I) which have a tacrine moiety connected to an heterocyclic moiety through a linker. Through careful selection of the substituents and the linker, the activity and selectivity towards acetylcholinesterase can be modulated. The compounds show potent AChE inhibition activities together with modifications in the .beta.-amyloid aggregation properties by binding simultaneously to the catalytic and peripheral AChE sites. They are useful in the treatment of AChE mediated diseases, such as the Alzheimer~s disease.

L'invention se rapporte à des composés représentés par la formule (I), qui possèdent une fraction tacrine reliée à une fraction hétérocyclique par l'intermédiaire d'un lieur. Il est possible de moduler l'activité et la sélectivité envers l'acétylcholinestérase en sélectionnant soigneusement les substituants et le lieur. Ces composés présentent de puissantes activités d'inhibition de l'AChE ainsi que des modifications des propriétés d'agrégation des .beta.-amyloïdes par liaison simultanée aux sites catalytiques et périphériques de l'AchE. Ces composés sont utiles pour le traitement des maladies médiées par l'AchE, telles que la maladie d'Alzheimer.

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