1,4-oxazepines as bace1 and/or bace2 inhibitors
AssigneeHoffmann-La Roche Inc.
InventorsEmanuele Gabellieri, Wolfgang Guba, Hans Hilpert, Harald Mauser, Alexander V. Mayweg, Mark Rogers-Evans, Didier Rombach, Andrew Thomas, Thomas Woltering, Wolfgang Wostl
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Abstract
The present invention relates to 1,4-Oxazepines 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.
Claims28
A compound of formula I,
- wherein
- R1 is selected from the group consisting of
- hydrogen,
- halogen, and
- C1-6-alkyl;
- R2 is selected from the group consisting of
- hydrogen,
- C1-6-alkyl, and
- halogen-C1-6-alkyl;
- R3 is selected from the group consisting of
- halogen,
- hydrogen, and
- C1-6-alkyl;
- R4 is selected from the group consisting of
- hydrogen and
- halogen;
- R5 is selected from the group consisting of
- hydrogen and
- C1-6-alkyl;
- R6 is selected from the group consisting of
- hydrogen and
- C1-6-alkyl;
- R7 is selected from the group consisting of
- halogen and
- C1-6-alkyl;
- n is 0 or 1;
- and
- R8 is selected from the group consisting of
- heteroaryl,
- heteroaryl, substituted by 1-4 substituents individually selected from the group consisting of cyano, cyano-C1-6-alkyl, halogen, halogen-C1-6-alkyl, halogen-C1-6-alkoxy, C1-6-alkoxy and C1-6-alkyl,
- heteroaryl-CH2—,
- heteroaryl-CH2—, substituted by 1-4 substituents individually selected from the group consisting of cyano, cyano-C1-6-alkyl, halogen, halogen-C1-6-alkyl, halogen-C1-6-alkoxy, C1-6-alkoxy and C1-6-alkyl,
- aryl,
- aryl, substituted by 1-4 substituents individually selected from the group consisting of cyano, cyano-C1-6-alkyl, halogen, halogen-C1-6-alkyl, halogen-C1-6-alkoxy, C1-6-alkoxy and C1-6-alkyl,
- heterocyclyl, and
- heterocyclyl, substituted by 1-4 substituents individually selected from the group consisting of cyano, cyano-C1-6-alkyl, halogen, halogen-C1-6-alkyl, halogen-C1-6-alkoxy, C1-6-alkoxy and C1-6-alkyl;
- or a pharmaceutically acceptable salt thereof.
A pharmaceutical composition comprising a therapeutically effective amount of a compound of formula I
- wherein
- R1 is selected from the group consisting of
- hydrogen,
- halogen, and
- C1-6-alkyl;
- R2 is selected from the group consisting of
- hydrogen,
- C1-6-alkyl, and
- halogen-C1-6-alkyl;
- R3 is selected from the group consisting of
- halogen,
- hydrogen, and
- C1-6-alkyl;
- R4 is selected from the group consisting of
- hydrogen and
- halogen;
- R5 is selected from the group consisting of
- hydrogen and
- C1-6-alkyl;
- R6 is selected from the group consisting of
- hydrogen and
- C1-6-alkyl;
- R7 is selected from the group consisting of
- halogen and
- C1-6-alkyl;
- n is 0 or 1;
- and
- R8 is selected from the group consisting of
- heteroaryl,
- heteroaryl, substituted by 1-4 substituents individually selected from the group consisting of cyano, cyano-C1-6-alkyl, halogen, halogen-C1-6-alkyl, halogen-C1-6-alkoxy, C1-6-alkoxy and C1-6-alkyl,
- heteroaryl-CH2—,
- heteroaryl-CH2—, substituted by 1-4 substituents individually selected from the group consisting of cyano, cyano-C1-6-alkyl, halogen, halogen-C1-6-alkyl, halogen-C1-6-alkoxy, C1-6-alkoxy and C1-6-alkyl,
- aryl,
- aryl, substituted by 1-4 substituents individually selected from the group consisting of cyano, cyano-C1-6-alkyl, halogen, halogen-C1-6-alkyl, halogen-C1-6-alkoxy, C1-6-alkoxy and C1-6-alkyl,
- heterocyclyl, and
- heterocyclyl, substituted by 1-4 substituents individually selected from the group consisting of cyano, cyano-C1-6-alkyl, halogen, halogen-C1-6-alkyl, halogen-C1-6-alkoxy, C1-6-alkoxy and C1-6-alkyl;
- or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.
Dependencies are inferred from the claim text.