Tricyclic indole hydroxyethylamine derivatives and their use...

C - Chemistry – Metallurgy – 07 – D

Patent

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Details

C07D 513/06 (2006.01) A61K 31/554 (2006.01) A61P 25/28 (2006.01) C07D 209/00 (2006.01) C07D 281/00 (2006.01)

Patent

CA 2549072

The present invention relates to novel hydroxyethylamine compounds having Asp2 (.beta.-secretase, BACE1 or Memapsin) inhibitory activity of formula (I), processes for their preparation, to compositions containing them and to their use in the treatment of diseases characterised by elevated .beta.-amyloid levels or .beta.-amyloid deposits, particularly Alzheimer's disease. Formula (I) wherein, inter alia, A-B represents -NR5-SO2- or -NR5-CO-; R5 represents hydrogen, C1-6alkyl, C3-6 alkenyl, C3-6 alkynyl, C3-10 cycloalkyl, -C0-6 alkylaryl, -C0-6 alkyl-heteroaryl, -C0-6 alkyl-heterocyclyl, -C3-10 cycloalkyl- aryl or -C3-10 cycloalkyl-heteroaryl; -W- represents -CH2-, -(CH2)2-, -(CH2)3- , -C(H)=C(H)- or -CH2-C(H)=C(H)-; X-Y-Z represents -C=CR8-NR9-;

L'invention concerne de nouveaux composés hydroxyéthylamine ayant une activité inhibant Asp2(.beta.-secrétase, BACE1 ou Memapsine) de formule (I), des procédés permettant de les préparer, des compositions les contenant, ainsi que leur utilisation dans le traitement de pathologies caractérisées par des taux élevés de .beta.-amyloïde ou de dépôts de .beta.- amyloïde, notamment la maladie d'Alzheimer. Dans cette formule, entre autres, A-B désigne NR?5¿-SO¿2?- ou NR?5¿-CO- ; R?5¿ désigne hydrogène, alkyle C¿1-6?. alkényle C¿3-6?, alkynyle C¿3-6?, cycloalkyle C¿3-10?, alkyle-aryle C¿0-6?, alkyle-hétéroaryle C¿0-6?, alkyle-hétérocyclyle C¿0-6?, cycloalkyle-aryle C¿3-10 ?ou cycloalkyle-hétéroaryle C¿3-10?; -W- désigne CH¿2?-, -(CH¿2?)¿2?-, -(CH¿2?)¿3?-, -C(H)=C(H)- ou CH¿2?-C(H)=C(H)- ; X-Y-Z désigne C=CR?8¿-NR?9¿-.¿ ?

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