Trifluoromethylpropanamide derivatives

Patent metadata

Field	Value
Publication number	US-9980929-B2
Application number	US-201715683341-A
Country	US
Kind code	B2
Filing date	Aug 22, 2017
Priority date	Feb 25, 2015
Publication date	May 29, 2018
Grant date	May 29, 2018

Abstract

The invention provides novel compounds having the general formula (I)

wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and R 7 are as described herein, compositions including the compounds and methods of using the compounds.

First claim

We claim:

1. A compound of formula (I)

wherein
R 1 is alkyl, haloalkyl or cycloalkyl;
R 2 is hydrogen, alkyl, haloalkyl or cycloalkyl;
R 3 is hydrogen, alkyl or cycloalkyl;
R 4 is optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroaryl or optionally substituted heteroarylalkyl, wherein each moiety is optionally substituted by one to three substituents independently selected from halogen, alkyl, haloalkyl, cycloalkyl, cyano, hydroxy, alkoxy or haloalkoxy;
R 5 is H, alkyl, haloalkyl or cycloalkyl;
R 6 is H, alkyl or cycloalkyl;
R 7 is optionally substituted adamantanylalkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted dicycloalkylalkyl, optionally substituted heterocycloalkylarylalkyl, optionally substituted aryloxycycloalkylalkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted arylalkenyl, optionally substituted diarylalkyl, optionally substituted aryloxyalkyl, optionally substituted diaryloxyalkyl, optionally substituted arylaryloxyalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, optionally substituted arylheteroarylalkyl or optionally substituted aryloxyheteroarylalkyl, wherein the optional substituents are one to three groups independently selected from halogen, alkyl, haloalkyl, cycloalkyl, cyano, hydroxy, alkoxy, haloalkoxy or phenyl;
or a pharmaceutically acceptable salt thereof.

2. The compound according to claim 1 , wherein
R 1 is alkyl, haloalkyl or cycloalkyl;
R 2 is hydrogen, alkyl, haloalkyl or cycloalkyl;
R 3 is hydrogen, alkyl or cycloalkyl;
R 4 is optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroaryl or optionally substituted heteroarylalkyl, wherein the optional substituents are one to three groups independently selected from halogen, alkyl, haloalkyl, cycloalkyl, cyano, hydroxy, alkoxy or haloalkoxy;
R 5 is hydrogen, alkyl, haloalkyl or cycloalkyl;
R 6 is hydrogen, alkyl or cycloalkyl;
R 7 is optionally substituted adamantanylalkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted dicycloalkylalkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted arylalkenyl, optionally substituted diarylalkyl, optionally substituted aryloxyalkyl, optionally optionally substituted diaryloxyalkyl, optionally substituted arylaryloxyalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, optionally substituted arylheteroarylalkyl or optionally substituted aryloxyheteroarylalkyl, wherein the optional substituents are one to three groups independently selected from halogen, alkyl, haloalkyl, cycloalkyl, cyano, hydroxy, alkoxy, haloalkoxy or phenyl;
or a pharmaceutically acceptable salt thereof.

3. The compound according to claim 1 wherein R 1 is alkyl.

4. The compound according to claim 1 wherein R 2 is hydrogen.

5. The compound according to claim 1 wherein R 3 is hydrogen and alkyl.

6. The compound according to claim 1 wherein R 3 is hydrogen.

7. The compound according to claim 1 wherein R 4 is optionally substituted phenyl, optionally substituted phenylalkyl or optionally substituted pyridinylalkyl, wherein the optional substituents are one to three groups independently selected from alkoxy or halogen.

8. The compound according to claim 7 wherein R 4 phenylalkyl optionally substituted by one halogen or phenyl optionally substituted by one alkoxy.

9. The compound according to claim 8 wherein R 4 is phenylmethyl, phenyl, methoxyphenyl or chlorophenylmethyl.

10. The compound according to claim 1 wherein R 1 is alkyl, R 2 is hydrogen, R 3 is hydrogen or alkyl, and R 4 is phenylalkyl optionally substituted by one halogen or phenyl optionally substituted by one alkoxy.

11. The compound according to claim 1 wherein R 5 is hydrogen.

12. The compound according to claim 1 wherein R 6 is hydrogen.

13. The compound according to claim 1 wherein R 1 is alkyl, R 2 , R 5 and R 6 are hydrogen, R 3 is hydrogen or alkyl and R 4 phenylalkyl optionally substituted by one halogen or phenyl optionally substituted by one alkoxy.

14. The compound according to claim 1 wherein R 7 is optionally substituted adamantanylalkyl, optionally substituted cycloalkylalkyl, optionally substituted 1,1-dioxo-1,4-thiazinanylphenylalkyl, optionally substituted phenoxycycloalkylalkyl, optionally substituted phenylalkyl, optionally substituted phenylalkenyl, optionally substituted diphenylalkyl, optionally substituted phenoxyalkyl, optionally substituted phenylphenoxyalkyl, optionally substituted benzofuranyl or optionally substituted benzothiophenyl, wherein the optional substituents are one to three groups independently selected from halogen, alkoxy or phenyl.

15. The compound according to claim 1 wherein R 7 is optionally substituted adamantanylalkyl, optionally substituted cycloalkylalkyl, optionally substituted phenylalkyl, optionally substituted phenylalkenyl, optionally substituted diphenylalkyl, optionally substituted phenoxyalkyl, optionally substituted phenylphenoxyalkyl, optionally substituted benzofuranyl or optionally substituted benzothiophenyl, wherein the optional substituents are one to three groups independently selected from halogen, alkoxy or phenyl.

16. The compound according to claim 1 wherein R 7 is, dichlorophenoxymethyl, dichlorophenylethyl, 1,1-dioxo-1,4-thiazinanyl-dichlorophenylethyl or dichlorophenylethylenyl.

17. The compound according to claim 1 wherein R 7 is dichlorophenoxymethyl or dichlorophenylethylenyl.

18. The compound according to claim 1 wherein the compound is of formula (Ia)

19. The compound according to claim 1 wherein
R 1 is alkyl;
R 2 , R 3 , R 5 and R 6 are hydrogen;
R 4 is phenylalkyl optionally substituted by one halogen or phenyl optionally substituted by one alkoxy;
R 7 is optionally substituted 1,1-dioxo-1,4-thiazinanylphenylalkyl, optionally substituted phenylalkyl, optionally substituted phenylalkenyl, optionally substituted diphenylalkyl, optionally substituted phenoxyalkyl or optionally substituted phenylphenoxyalkyl, wherein the optional substituents are one to three independently selected halogens;
or, a pharmaceutically acceptable salt thereof.

20. The compound according to claim 18 wherein
R 1 is alkyl;
R 2 , R 3 , R 5 and R 6 are hydrogen;
R 4 is phenylalkyl optionally substituted by a halogen or phenyl optionally substituted by one alkoxy;
R 7 is optionally substituted 1,1-dioxo-1,4-thiazinanylphenylalkyl, optionally substituted phenylalkyl, optionally substituted phenylalkenyl, optionally substituted diphenylalkyl, optionally substituted phenoxyalkyl or optionally substituted phenylphenoxyalkyl, wherein the optional substituents are one to three groups independently selected halogen substituents;
or, a pharmaceutically acceptable salt thereof.

21. The compound according to claim 1 wherein
R 1 is alkyl;
R 2 , R 3 , R 5 and R 6 are hydrogen;
R 4 is phenylalkyl optionally substituted by one halogen or phenyl o

Assignees

• Hoffmann La Roche
• Hoffmann La Roche

Inventors

• Hornsperger Benoit
• Iacone Roberto
• Kuhn Bernd
• Maerki Hans P
• Mohr Peter
• Reutlinger Michael

Classifications

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P27/02

  Ophthalmic agents · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title