BACE1 inhibitors

摘要

The present invention provides a compound of formula I, having BACE1 inhibitory activity, their manufacture, pharmaceutical compositions containing them and their use as therapeutically active substances. The active compounds of the present invention are useful in the therapeutic and/or prophylactic treatment of e.g. Alzheimer's disease.

主权项

1. A compound of formula I: wherein: n is 1, 2 or 3; R1 is selected from the group consisting of
i) C1-6-alkyl andii) halogen-C1-6-alkyl; R2 is selected from the group consisting of
i) C1-6-alkyl, andii) halogen-C1-6-alkyl; or R1 and R2 form together with the C-atom they are attached to, a C3-6-cycloalkyl-, wherein the C3-6-cycloalkyl- is optionally substituted by one or more substituents selected from the group consisting of halogen and hydroxyl; R3 is each independently selected from the group consisting of
i) hydrogen,ii) C1-6-alkyl, andiii) halogen; R4 is each independently selected from the group consisting of
i) hydrogen,ii) C1-6-alkyl, andiii) halogen; or wherein R3 and R4 together are (CH2)m—, wherein m is 2, 3, 4 or 5, R5 is hydrogen, R6 is selected from the group consisting of
i) C1-6-alkyl, andii) halogen-C1-6-alkyl; R7 is selected from the group consisting of
i) hydrogen, andii) halogen; R8 is selected from the group consisting of
i) aryl,ii) aryl substituted by 1-4 substituents individually selected from amino, cyano, halogen, halogen-C1-6-alkyl, halogen-C1-6-alkoxy, C1-6-alkoxy, C1-6-alkoxy-C1-6-alkyl, C2-6-alkynyl-C1-6-alkoxy, C2-6-alkynyl, C1-6-alkyl, COOR9, wherein R9 is H or C1-6-alkyl, CONR10R11, wherein R10 is H or C1-6-alkyl C3-6-cycloalkyl and R11 is H or C1-6-alkyl, C3-6-cycloalkyl that is optionally substituted by 1 to 4 substituents individually selected from the group consisting of halogen, cyano, C1-6-alkyl and C1-6-alkoxy, C3-6-cycloalkyl-C1-6-alkoxy and C3-6-cycloalkyl-C1-6-alkoxy, wherein the cycloalkyl unit is substituted by 1 to 4 substituents individually selected from the group consisting of halogen, cyano, C1-6-alkyl and C1-6-alkoxy;iii) heteroaryl, andiv) heteroaryl substituted by 1-4 substituents individually selected from amino, cyano, halogen, halogen-C1-6-alkyl, halogen-C1-6-alkoxy, C1-6-alkoxy, C1-6-alkoxy-C1-6-alkyl, C2-6-alkynyl-C1-6-alkoxy, C2-6-alkynyl, C1-6-alkyl, COOR9, wherein R9 is H or C1-6-alkyl, CONR10R11, wherein R10 is H or C1-6-alkyl C3-6-cycloalkyl and R11 is H or C3-6-cycloalkyl that is optionally substituted by 1 to 4 substituents individually selected from the group consisting of halogen, cyano, C1-6-alkyl and C1-6-alkoxy, C3-6-cycloalkyl-C1-6-alkoxy and C3-6-cycloalkyl-C1-6-alkoxy, wherein the cycloalkyl unit is substituted by 1 to 4 substituents individually selected from the group consisting of halogen, cyano, C1-6-alkyl and C1-6-alkoxy; or pharmaceutically acceptable salts thereof.