Novel gamma secretase inhibitors

Details Novel gamma secretase inhibitors Novel gamma secretase inhibitors

C - Chemistry, Metallurgy

07

D

C07D 401/06 (2006.01) A61K 31/44 (2006.01) A61P 25/28 (2006.01) C07D 401/14 (2006.01) C07D 471/04 (2006.01)

Patent

CA 2563033

Gamma-secretase inhibitors of the formula: Chemical formula should be inserted here as it appears on the abstract in paper form. are useful in treating various neurodegenerative diseases, wherein, for example: R1 includes unsubstituted or substituted aryl or heteroaryl groups; R2 includes -C(O)-Y, alkylene-C(O)-Y, alkylene-cycloalkylene-C(O)-Y, cycloalkylene-alkylene-C(O)-Y, alkylene cycloalkylene-alkylene-C(O)-Y, cycloalkylene-C(O)-Y, -S(O)-Y, alkylene-S(O)-Y, alkylene-cycloalkylene-S(O)-Y, cycloalkylene-alkylene-S(O)-Y, alkylene cycloalkylene-alkylene-S(O)-Y, cycloalkylene-S(O)-Y, -S(O2)-Y, alkylene-S(O2)-Y, alkylene cycloalkylene S(O2)-Y, cycloalkylene alkylene S(O2)- Y, alkylene cycloalkylene-alkylene-S(O2)-Y, and cycloalkylene-S(O2)-Y, wherein Y is as defined herein, and each of said alkylene or cycloalkylene may be unsubstituted or substituted as provided herein; each R3 is independently includes H, alkyl, O alkyl, OH, N(R9)2, acyl, and aroyl; or the moiety (R3)2, together with the ring carbon atom to which it is shown attached in formula I, defines a carbonyl group, -C(O)-; each R3A and R3B independently includes H, or alkyl; R11 includes aryl, heteroaryl, alkyl, cycloalkyl, arylalkyl, arylcycloalkyl, heteroarylalkyl, heteroarylcycloalkyl, arylheterocycloalkyl, or alkoxyalkyl. One or more of the compounds of formula I, or pharmaceutically acceptable salts, solvates, and/or esters, or compositions comprised thereof, may be used to treat, e.g., Alzheimer's Disease.

L'invention concerne des inhibiteurs de gamma secrétases de la formule (I) lesquels sont utiles pour traiter diverses maladies neurodégénératives, dans laquelle, par exemple: R?1¿ comprend des groupes aryle ou hétéroaryle non substitués ou substitués; R?2¿ comprend -C(O)-Y, alkylène-C(O)-Y, alkylène-cycloalkylène-C(O)-Y, cycloalkylène-alkylène-C(O)-Y, alkylène cycloalkylène-alkylène-C(O)-Y, cycloalkylène-C(O)-Y, -S(O)-Y, alkylène-S(O)-Y, alkylène-cycloalkylène-S(O)-Y, cycloalkylène-alkylène-S(O)-Y, alkylène cycloalkylène-alkylène-S(O)-Y, cycloalkylène-S(O)-Y, -S(O¿2?)-Y, alkylène-S(O¿2?)-Y, alkylène cycloalkylène S(O¿2?)-Y, cycloalkylène alkylène S(O¿2?)-Y, alkylène cycloalkylène-alkylène-S(O¿2?)-Y, et cycloalkylène-S(O¿2?)-Y, où Y a la notation ci-définie, chacun desdits alkylène ou cycloalkylène peut être non substitué ou substitué tel qu'ici prévu; chaque R?3¿ comprend indépendamment H, alkyle, -O-alkyle, -OH, -N(R?9¿)¿2?, acyle, et aroyle; ou la fraction (R?3¿)¿2?, avec l'atome de carbone cyclique auquel elle est illustrée comme étant fixée dans la formule (I), définit un groupe carbonyle, - C(O)-; chaque R?3A¿ et R?3B¿ contient indépendamment H ou alkyle; R?11¿ contient aryle, hétéroaryle, alkyle, cycloalkyle, arylalkyle, arylcycloalkyle, hétéroarylalkyle, hétéroarylcycloalkyle, arylhétérocycloalkyle, ou alkoxyalkyle. Un ou plusieurs des composés de la formule (I) ou leurs sels, solvates et/ou esters pharmaceutiquement acceptables, ou les compositions les contenant, peuvent être utilisés pour traiter, par exemple, la maladie d'Alzheimer.

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