Pyridyl-triazabicycles
US-10414780-B2 · Sep 17, 2019 · US
BACE1 inhibitors
US10696691B2 · US · B2
| Field | Value |
|---|---|
| Publication number | US-10696691-B2 |
| Application number | US-201916274911-A |
| Country | US |
| Kind code | B2 |
| Filing date | Feb 13, 2019 |
| Priority date | Aug 12, 2015 |
| Publication date | Jun 30, 2020 |
| Grant date | Jun 30, 2020 |
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Abstract
Official abstract text for this publication.
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.
First claim
Opening claim text (preview).
The invention claimed is: 1. A pharmaceutical composition, comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound selected from the group consisting of: N-(3-((3aR,4R,8S)-6-amino-4,7,7-trimethyl-8-oxido-3,3a,4,7-tetrahydro-2H-isothiazolo[1,5-a][1,4]thiazin-4-yl)-4-fluorophenyl)-5-cyano-3-methylpicolinamide, N-(3-((3aS,4R,8R)-6-amino-4,7,7-trimethyl-8-oxido-3,3a,4,7-tetrahydro-2H-isothiazolo[1,5-a][1,4]thiazin-4-yl)-4-fluorophenyl)-5-cyano-3-methylpicolinamide, N-(3-((3aS,4R,8R)-6-amino-4,7,7-trimethyl-8-oxido-3,3a,4,7-tetrahydro-2H-isothiazolo[1,5-a][1,4]thiazin-4-yl)-4-fluorophenyl)-3-chloro-5-cyanopicolinamide, N-(3-((3aS,4R,8R)-6-amino-4,7,7-trimethyl-8-oxido-3,3a,4,7-tetrahydro-2H-isothiazolo[1,5-a][1,4]thiazin-4-yl)-4-fluorophenyl)-3,5-dichloropicolinamide, N-(3-((3aS,4R,8R)-6-amino-4,7,7-trimethyl-8-oxido-3,3a,4,7-tetrahydro-2H-isothiazolo[1,5-a][1,4]thiazin-4-yl)-4-fluorophenyl)-2-chloro-4-cyanobenzamide, N-(3-((3aS,4R,8R)-6-amino-4,7,7-trimethyl-8-oxido-3,3a,4,7-tetrahydro-2H-isothiazolo[1,5-a][1,4]thiazin-4-yl)-4-fluorophenyl)-5-(difluoromethoxy)picolinamide, N-(3-((3aS,4R,8R)-6-amino-4,7,7-trimethyl-8-oxido-3,3a,4,7-tetrahydro-2H-isothiazolo[1,5-a][1,4]thiazin-4-yl)-4-fluorophenyl)-4-chloro-1-(difluoromethyl)-1H-pyrazole-3-carboxamide, N-(3-((3aS,4R,8R)-6-amino-4,7,7-trimethyl-8-oxido-3,3a,4,7-tetrahydro-2H-isothiazolo[1,5-a][1,4]thiazin-4-yl)-4-fluorophenyl)-5-(2,2-difluoroethoxy)pyrazine-2-carboxamide, N-(3-((3aS,4R,8R)-6-amino-4,7,7-trimethyl-8-oxido-3,3a,4,7-tetrahydro-2H-isothiazolo[1,5-a][1,4]thiazin-4-yl)-4-fluorophenyl)-3-chloro-5-(trifluoromethyl)picolinamide, N-(3-((3aS,4R,8R)-6-amino-4,7,7-trimethyl-8-oxido-3,3a,4,7-tetrahydro-2H-isothiazolo[1,5-a][1,4]thiazin-4-yl)-4-fluorophenyl)-4-cyano-2-methylbenzamide, N-(3-((3aS,4R,8R)-6-amino-4,7,7-trimethyl-8-oxido-3,3a,4,7-tetrahydro-2H-isothiazolo[1,5-a][1,4]thiazin-4-yl)-4-fluorophenyl)-5-(2,2-difluoroethoxy)picolinamide, N-(3-((3aS,4R,8R)-6-amino-4,7,7-trimethyl-8-oxido-3,3a,4,7-tetrahydro-2H-isothiazolo[1,5-a][1,4]thiazin-4-yl)-4-fluorophenyl)-5-(difluoromethoxy)-3-methylpicolinamide, N-(3-((3aS,4R,8R)-6-amino-4,7,7-trimethyl-8-oxido-3,3a,4,7-tetrahydro-2H-isothiazolo[1,5-a][1,4]thiazin-4-yl)-4-fluorophenyl)-5-(2,2,3,3-tetrafluoropropoxy)picolinamide, N-(3-((3aS,4R,8R)-6-amino-4,7,7-trimethyl-8-oxido-3,3a,4,7-tetrahydro-2H-isothiazolo[1,5-a][1,4]thiazin-4-yl)-4-fluorophenyl)-3-chloro-5-(difluoromethoxy)picolinamide, N-(3-((3aS,4R,8R)-6-amino-4,7,7-trimethyl-8-oxido-3,3a,4,7-tetrahydro-2H-isothiazolo[1,5-a][1,4]thiazin-4-yl)-4-fluorophenyl)-5-methoxypyrazine-2-carboxamide, N-(3-((3aS,4R,8R)-6-amino-4,7,7-trimethyl-8-oxido-3,3a,4,7-tetrahydro-2H-isothiazolo[1,5-a][1,4]thiazin-4-yl)-4-fluorophenyl)-5-(difluoromethoxy)pyrazine-2-carboxamide, N-(3-((3aS,4R,8R)-6-amino-4,7,7-trimethyl-8-oxido-3,3a,4,7-tetrahydro-2H-isothiazolo[1,5-a][1,4]thiazin-4-yl)-4-fluorophenyl)-5-cyanopicolinamide, N-(3-((3aS,4R,8R)-6-amino-4,7,7-trimethyl-8-oxido-3,3a,4,7-tetrahydro-2H-isothiazolo[1,5-a][1,4]thiazin-4-yl)-4-fluorophenyl)-5-fluoropicolinamide, N-(3-((3aS,4R,8R)-6-amino-4,7,7-trimethyl-8-oxido-3,3a,4,7-tetrahydro-2H-isothiazolo[1,5-a][1,4]thiazin-4-yl)-4-fluorophenyl)-5-chloropicolinamide, N-(3-((3aS,4R,8R)-6-amino-4,7,7-trimethyl-8-oxido-3,3a,4,7-tetrahydro-2H-isothiazolo[1,5-a][1,4]thiazin-4-yl)-4-fluorophenyl)-3,5-difluoropicolinamide, N-(3-((3aS,4R,8R)-6-amino-4,7,7-trimethyl-8-oxido-3,3a,4,7-tetrahydro-2H-isothiazolo[1,5-a][1,4]thiazin-4-yl)-4-fluorophenyl)-5-methylpicolinamide, N-(3-((3aS,4R,8R)-6-amino-4,7,7-trimethyl-8-oxido-3,3a,4,7-tetrahydro-2H-isothiazolo[1,5-a][1,4]thiazin-4-yl)-4-fluorophenyl)-2-methylpyrimidine-5-carboxamide, N-(3-((3aS,4R,8R)-6-amino-4,7,7-trimethyl-8-oxido-3,3a,4,7-tetrahydro-2H-isothiazolo[1,5-a][1,4]thiazin-4-yl)-4-fluorophenyl)-5-(2,2,3,3-tetrafluoropropoxy)pyrazine-2-carboxamide, N-(3-((3aS,4R,8R)-6-amino-4,7,7-trimethyl-8-oxido-3,3a,4,7-tetrahydro-2H-isothiazolo[1,5-a][1,4]thiazin-4-yl)-4-fluorophenyl)-3,5-dimethylpicolinamide, N-(3-((3aS,4R,8R)-6-amino-4,7,7-trimethyl-8-oxido-3,3a,4,7-tetrahydro-2H-isothiazolo[1,5-a][1,4]thiazin-4-yl)-4-fluorophenyl)-5-methoxypicolinamide, N-(3-((3aS,4R,8R)-6-amino-4,7,7-trimethyl-8-oxido-3,3a,4,7-tetrahydro-2H-isothiazolo[1,5-a][1,4]thiazin-4-yl)-4-fluorophenyl)-5-ethoxypicolinamide, N-(3-((3aS,4R,8R)-6-amino-4,7,7-trimethyl-8-oxido-3,3a,4,7-tetrahydro-2H-isothiazolo[1,5-a][1,4]thiazin-4-yl)-4-fluorophenyl)-5-methoxy-3-methylpicolinamide, and N-(3-((3aS,4R,8R)-6-amino-4,7,7-trimethyl-8-oxido-3,3a,4,7-tetrahydro-2H-isothiazolo[1,5-a][1,4]thiazin-4-yl)-4-fluorophenyl)-5-ethoxypyrazine-2-carboxamide, or pharmaceutically acceptable salts thereof. 2. The pharmaceutical composition according to claim 1 , wherein the compound is selected from the group consisting of: N-(3-((3aS,4R,8R)-6-amino-4,7,7-trimethyl-8-oxido-3,3a,4,7-tetrahydro-2H-isothiazolo[1,5-a][1,4]thiazin-4-yl)-4-fluorophenyl)-5-cyano-3-methylpicolinamide, N-(3-((3aR,4R,8S)-6-amino-4,7,7-trimethyl-8-oxido-3,3a,4,7-tetrahydro-2H-isothiazolo[1,5-a][1,4]thiazin-4-yl)-4-fluorophenyl)-5-cyano-3-methylpicolinamide, N-(3-((3aS,4R,8R)-6-amino-4,7,7-trimethyl-8-oxido-3,3a,4,7-tetrahydro-2H-isothiazolo[1,5-a][1,4]thiazin-4-yl)-4-fluorophenyl)-3-chloro-5-cyanopicolinamide, N-(3-((3aS,4R,8R)-6-amino-4,7,7-trimethyl-8-oxido-3,3a,4,7-tetrahydro-2H-isothiazolo[1,5-a][1,4]thiazin-4-yl)-4-fluorophenyl)-3,5-dichloropicolinamide, N-(3-((3aS,4R,8R)-6-amino-4,7,7-trimethyl-8-oxido-3,3a,4,7-tetrahydro-2H-isothiazolo[1,5-a][1,4]thiazin-4-yl)-4-fluorophenyl)-2-chloro-4-cyanobenzamide, N-(3-((3aS,4R,8R)-6-amino-4,7,7-trimethyl-8-oxido-3,3a,4,7-tetrahydro-2H-isothiazolo[1,5-a][1,4]thiazin-4-yl)-4-fluorophenyl)-5-(difluoromethoxy)picolinamide, N-(3-((3aS,4R,8R)-6-amino-4,7,7-trimethyl-8-oxido-3,3a,4,7-tetrahydro-2H-isothiazolo[1,5-a][1,4]thiazin-4-yl)-4-fluorophenyl)-4-chloro-1-(difluoromethyl)-1H-pyrazole-3-carboxamide, N-(3-((3aS,4R,8R)-6-amino-4,7,7-trimethyl-8-oxido-3,3a,4,7-tetrahydro-2H-isothiazolo[1,5-a][1,4]thiazin-4-yl)-4-fluorophenyl)-5-(2,2-difluoroethoxy)pyrazine-2-carboxamide, N-(3-((3aS,4R,8R)-6-amino-4,7,7-trimethyl-8-oxido-3,3a,4,7-tetrahydro-2H-isothiazolo[1,5-a][1,4]thiazin-4-yl)-4-fluorophenyl)-3-chloro-5-(trifluoromethyl)picolinamide, N-(3-((3aS,4R,8R)-6-amino-4,7,7-trimethyl-8-oxido-3,3a,4,7-tetrahydro-2H-isothiazolo[1,5-a][1,4]thiazin-4-yl)-4-fluorophenyl)-4-cyano-2-methylbenzamide, N-(3-((3aS,4R,8R)-6-amino-4,7,7-trimethyl-8-oxido-3,3a,4,7-tetrahydro-2H-isothiazolo[1,5-a][1,4]thiazin-4-yl)-4-fluorophenyl)-5-(2,2-difluoroethoxy)picolinamide, N-(3-((3aS,4R,8R)-6-amino-4,7,7-trimethyl-8-oxido-3,3a,4,7-tetrahydro-2H-isothiazolo[1,5-a][1,4]thiazin-4-yl)-4-fluorophenyl)-5-(difluoromethoxy)-3-methylpicolinamide, N-(3-((3aS,4R,8R)-6-amino-4,7,7-trimethyl-8-oxido-3,3a,4,7-tetrahydro-2H-isothiazolo[1,5-a][1,4]thiazin-4-yl)-4-fluorophenyl)-5-(2,2,3,3-tetrafluoropropoxy)picolinamide, N-(3-((3aS,4R,8R)-6-amino-4,7,7-trimethyl-8-oxido-3,3a,4,7-tetrahydro-2H-isothiazolo[1,5-a][1,4]thiazin-4-yl)-4-fluorophenyl)-3-chloro-5-(difluoromethoxy)picolinamide, and N-(3-((3aS,4R,8R)-6-amino-4,7,7-trimethyl-8-oxido-3,3a,4,7-tetrahydro-2H-isothiazolo[1,5-a][1,4]thiazin-4-yl)-4-fluorophenyl)-5-methoxypyrazine-2-carboxamide, or pharmaceutically acceptable salts thereof. 3. The pharmaceutical composition according to claim 2 , wherein the compound is selected from the group consisting of: N-(3-((3aS,4R,8R)-6-amino-4,7,7-trimethyl-8-oxido-3,3a,4,7-tetrahydro-2H-isothiazolo[1,5-a][1,4]thiazin-4-yl)-4-fluorophenyl)-5-cyano-3-methylpicolinamide and N-(3-((3aR,4R,8S)-6-amino-4,7,7-trimethyl-8-oxido-3,3a,4,7-tetrahydro-2H-isothiazolo[1,5-a][1,4]thiazin-4-yl)-4-fluorophenyl)-5-cyano-3-methylpicolinamide, or pharmaceutically acceptable salts thereof. 4. A method for treating diseases and disor
Assignees
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for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia · CPC title
- C07D513/04Primary
Ortho-condensed systems · CPC title
ortho- or peri-condensed with heterocyclic ring systems · CPC title
Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title
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- What does patent US10696691B2 cover?
- 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.
- Who is the assignee on this patent?
- Hoffmann La Roche
- What technology area does this patent fall under?
- Primary CPC classification C07D513/04. Mapped technology areas include Chemistry & Metallurgy.
- When was this patent published?
- Publication date Tue Jun 30 2020 00:00:00 GMT+0000 (Coordinated Universal Time) (B2). Legal status and post-grant events are not shown on this page.
- What related patents are in patentsdb?
- We list 8 related publications on this page (citations in our corpus or others sharing the same primary CPC).