Back to results
US 9,067,924 B2Granted
1,4 thiazepines/sulfones as BACE1 and/or BACE2 inhibitors
AssigneeHoffmann-La Roche Inc.
InventorsHans Hilpert, Mark Rogers-Evans, Didier Rombach
Life of this patent
Estimating the term…
Abstract
The present invention relates to 1,4 Thiazepines/Sulfones 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.
Claims23
A compound of formula
- 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
- hydrogen and
- C1-6-alkyl;
- R4 is selected from the group consisting of
- hydrogen and
- C1-6-alkyl;
- R5 is heteroaryl unsubstituted or substituted by one or two substituents individually selected from the group consisting of
- C1-6-alkyl,
- halogen,
- C1-6-alkoxy, and
- halogen-C1-6-alkyl;
- R6 is hydrogen;
- R7 is hydrogen;
- R8 is hydrogen;
- R9 is hydrogen;
- or R6 and R8 together form a 5-6 membered heterocyclyl;
- and
- X is selected from the group consisting of
- —S and
- —SO2;
- or a pharmaceutically acceptable salt thereof.
27 more elements
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,
- C1-5-alkyl, and
- halogen-C1-6-alkyl;
- R3 is selected from the group consisting of
- hydrogen and
- C1-6-alkyl;
- R4 is selected from the group consisting of
- hydrogen and
- C1-6-alkyl;
- R5 is heteroaryl unsubstituted or substituted by one or two substituents individually selected from the group consisting of
- C1-6-alkyl
- halogen,
- C1-6-alkoxy, and
- halogen-C1-6-alkyl;
- R6 is hydrogen;
- R7 is hydrogen;
- R8 is hydrogen;
- R9 is hydrogen;
- or R6 and R8 together form a 5-6 membered heterocyclyl;
- and
- X is selected from the group consisting of
- —S and
- —SO2;
- or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.
27 more elements
A compound, selected from the group consisting of
- 5-Cyano-pyridine-2-carboxylic acid [3-((S)-3-amino-2,2,5-trimethyl-1,1-dioxo-2,5,6,7-tetrahydro-1H-1λ6-[1,4]thiazepin-5-yl)-4-fluoro-phenyl]-amide,
- 5-Cyano-pyridine-2-carboxylic acid [3-((S)-3-amino-5-difluoromethyl-1,1-dioxo-2,5,6,7-tetrahydro-1H-1λ6-[1,4]thiazepin-5-yl)-4-fluoro-phenyl]-amide, and
- 5-Cyano-pyridine-2-carboxylic acid [3-((3aR,8S,8aS)-rel-6-amino-8-methyl-4,4-dioxo-3,3a,4,5,8,8a-hexahydro-1H-2-oxa-[[4λ6]]4λ6-thia-7-aza-azulen-8-yl)-4-fluoro-phenyl]-amide,
- or a pharmaceutical acceptable salt thereof.
1 more element
Dependencies are inferred from the claim text.