1,3-oxazines as BACE 1 and/or BACE2 inhibitors

摘要

The present invention provides compounds of formula I;
having BACE1 and/or BACE2 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 and type 2 diabetes.

主权项

1. A compound of formula I, wherein X is selected from the group consisting of
aryl,aryl substituted by 1-2 substituents individually selected from R1,heteroaryl,heteroaryl substituted by 1-2 substituents individually selected from R1 and halogen-aryl,C3-6-cycloalkyl, andC3-6-cycloalkyl substituted by 1-2 substituents individually selected from R1; Y is selected from the group consisting of
—C═O—NH—,—CH2—,—NH——NH—CHR7—,—O—CH2—, andabsent; Z is selected from the group consisting of
aryl,aryl substituted by 1-2 substituents individually selected from R8,heteroaryl,heteroaryl substituted by 1-2 substituents individually selected from R8,C3-6-cycloalkyl,C3-6-cycloalkyl substituted by 1-2 substituents individually selected from R8,heterocyclyl,heterocyclyl substituted by 1-2 substituents individually selected from R8,C2-6-alkynyl,C1-6-alkyl, andC1-6-alkyl substituted by 1-3 substituents individually selected from R9; R1 is selected from the group consisting of
hydrogen,halogen, andC1-6-alkyl; R2 is selected from the group consisting of
hydrogen,C1-6-alkyl, andhalogen-C1-3-alkyl; R3 is selected from the group consisting of
hydrogen,halogen, andC1-6-alkyl; R4 is selected from the group consisting of
hydrogenhalogen, andC1-6-alkyl; R5 is selected from the group consisting of
hydrogen andC1-6-alkyl; R6 is selected from the group consisting of
hydrogen andC1-6-alkyl; R7 is selected from the group consisting of
hydrogen andC1-6-alkyl; R8 is selected from the group consisting of
halogen,cyano,C1-6-alkyl,halogen-C1-6-alkyl,C1-6-alkoxy,halogen-C1-6-alkoxy,aryl,halogen-aryl, andC3-6-cycloalkyl; and R9 is selected from the group consisting of
halogen,cyano,C1-6-alkoxy, andhalogen-C1-6-alkoxy; or a pharmaceutically acceptable salt thereof.