Selective BACE1 inhibitors

Patent metadata

Field	Value
Publication number	US-9522923-B2
Application number	US-201615045305-A
Country	US
Kind code	B2
Filing date	Feb 17, 2016
Priority date	Feb 23, 2015
Publication date	Dec 20, 2016
Grant date	Dec 20, 2016

Abstract

The present invention provides a compound of Formula II:

or a pharmaceutically acceptable salt thereof, that are inhibitors of BACE.

First claim

We claim:

1. A compound of the formula:

wherein R is methyl, ethyl, or cyclopropyl;
or a pharmaceutically acceptable salt thereof.

2. The compound or salt thereof according to claim 1 wherein R is methyl.

3. The compound or salt thereof according to claim 2 wherein the compound is:

4. The compound or salt thereof according to claim 3 wherein the compound is:

5. The compound according to claim 4 which is:

6. The salt according to claim 4 which is:

7. The salt according to claim 4 which is:

8. The compound according to claim 4 which is:

9. The compound or salt thereof according to claim 4 wherein the compound is N-[3-[(4aS,5S,7aS)-2-amino-5-(1,1-difluoroethyl)-4,4a,5,7-tetrahydrofuro[3,4-d][1,3]thiazin-7a-yl]-4-fluoro-phenyl]-5-(1,2,4-triazol-1-yl)pyrazine-2-carboxamide.

10. The compound according to claim 5 which is N-[3-[(4aS,5S,7aS)-2-amino-5-(1,1-difluoroethyl)-4,4a,5,7-tetrahydrofuro[3,4-d][1,3]thiazin-7a-yl]-4-fluoro-phenyl]-5-(1,2,4-triazol-1-yl)pyrazine-2-carboxamide.

11. The compound according to claim 4 which is N-[3-[(4aS,5S,7aS)-2-amino-5-(1,1-difluoroethyl)-4,4a,5,7-tetrahydrofuro[3,4-d][1,3]thiazin-7a-yl]-4-fluoro-phenyl]-5-(1,2,4-triazol-1-yl)pyrazine-2-carboxamide hydrate.

12. The salt according to claim 4 which is N-[3-[(4aS,5S,7aS)-2-amino-5-(1,1-difluoroethyl)-4,4a,5,7-tetrahydrofuro[3,4-d][1,3]thiazin-7a-yl]-4-fluoro-phenyl]-5-(1,2,4-triazol-1-yl)pyrazine-2-carboxamide 4-methylbenzenesulfonate.

13. The salt according to claim 4 which is N-[3-[(4aS,5S,7aS)-2-amino-5-(1,1-difluoroethyl)-4,4a,5,7-tetrahydrofuro[3,4-d][1,3]thiazin-7a-yl]-4-fluoro-phenyl]-5-(1,2,4-triazol-1-yl)pyrazine-2-carboxamide malonate.

14. A method of treating Alzheimer's disease in a patient, comprising administering to a patient in need of such treatment an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof.

15. A method of treating the progression of mild cognitive impairment to Alzheimer's disease in a patient, comprising administering to a patient in need of such treatment an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof.

16. A pharmaceutical composition, comprising a compound or a pharmaceutically acceptable salt thereof according to claim 1 with one or more pharmaceutically acceptable carriers, diluents, or excipients.

17. A process for preparing a pharmaceutical composition, comprising admixing a compound or a pharmaceutically acceptable salt thereof according to claim 1 with one or more pharmaceutically acceptable carriers, diluents, or excipients.

Assignees

• Lilly Co Eli

Inventors

• Richards Simon James
• Hembre Erik James
• Lopez Jose Eduardo
• Winneroski Jr Leonard Larry
• Woods Timothy Andrew
• McMahon Jennifer Anne

Classifications

• A61P25/28

  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

• C07C309/30

  of six-membered aromatic rings substituted by alkyl groups · CPC title

• A61K31/542

  ortho- or peri-condensed with heterocyclic ring systems · CPC title

• C07C55/08

  Malonic acid · CPC title

• C07D513/04 Primary

  Ortho-condensed systems · CPC title