RU2011153772A

RU2011153772A - Fluorinated Aminotriazole Derivatives

Info

Publication number: RU2011153772A
Application number: RU2011153772/04A
Authority: RU
Inventors: Даниель БУР; Оливье КОРМЕНБЁФ; Сильвене КРЕН; Коринна ГРИСОСТОМИ; Ксавьер ЛЕРОЙ; Сильвья РИШАР-БИЛЬДШТАЙН
Original assignee: Актелион Фармасьютиклз Лтд
Priority date: 2009-06-09
Filing date: 2010-06-07
Publication date: 2013-07-20

Claims

1. The compound of formula (I)

,

where A represents a heteroaryl group, where two points of attachment of said heteroaryl group are in the 1,3-position;

R ¹ represents phenyl, which is unsubstituted, mono - or disubstituted, where the substituents are independently selected from the group consisting of halogen, methyl, methoxy, trifluoromethyl, trifluoromethoxy and dimethylamino; and

R ² represents hydrogen, methyl, ethyl or cyclopropyl; or a salt of such a compound.

2. The compound of formula (I) according to claim 1, where

A represents a group selected from furanyl, oxazolyl and thiazolyl, where two points of attachment of this group are in the 1,3-position;

R ¹ represents phenyl, which is unsubstituted, mono - or disubstituted, where the substituents are independently selected from the group consisting of fluoro, chloro, methyl, methoxy, trifluoromethyl, trifluoromethoxy and dimethylamino; and

R ² represents hydrogen, methyl or ethyl; or a salt of such a compound.

3. The compound of formula (I) according to one of claims 1 or 2, where

A is furan-2,5-diyl, oxazole-2,4-diyl or thiazole-2,4-diyl; or a salt of such a compound.

4. The compound of formula (I) according to one of claims 1 or 2, where

A is furan-2,5-diyl; or a salt of such a compound.

5. The compound of formula (I) according to one of claims 1 or 2, where

A is oxazole-2,4-diyl; or a salt of such a compound.

6. The compound of formula (I) according to one of claims 1 or 2, where

A is thiazole-2,4-diyl; or a salt of such a compound.

7. The compound of formula (I) according to one of claims 1 or 2, where

R ¹ represents unsubstituted phenyl; or a salt of such a compound.

8. The compound of formula (I) according to one of claims 1 or 2, where

R ¹ represents phenyl, which is monosubstituted fluorine, chlorine, methyl or trifluoromethyl; or a salt of such a compound.

9. The compound of formula (I) according to claim 4, where

10. The compound of formula (I) according to claim 5, where

11. The compound of formula (I) according to claim 6, where

12. The compound of formula (I) according to claim 8, where

R ² represents hydrogen; or a salt of such a compound.

13. The compound of formula (I) according to claim 8, where

R ² represents methyl or ethyl; or a salt of such a compound.

14. The compound of formula (I) according to claim 9, where

R ² represents methyl or ethyl; or a salt of such a compound.

15. The compound of formula (I) according to claim 10, where

R ² represents methyl or ethyl; or a salt of such a compound.

16. The compound of formula (I) according to claim 11, where

R ² represents methyl or ethyl; or a salt of such a compound.

17. The compound of formula (I) according to claim 1, selected from the group including:

{2- [5- (1,1-Difluoroethyl) furan-2-ylmethyl] -2H- [1,2,3] triazol-4-yl} 2-methyl-5-m-tolyloxazole-4-carboxylic acid amide ;

5-phenyloxazole-4-carboxylic acid {2- [4- (1,1-difluoroethyl) thiazol-2-ylmethyl] -2H- [1,2,3] triazol-4-yl} amide;

{2- [4- (1,1-Difluoroethyl) thiazol-2-ylmethyl] -2H- [1,2,3] triazol-4-yl} 2-methyl-5-m-tolyloxazole-4-carboxylic acid amide ;

{2- [5- (1,1-Difluoroethyl) furan-2-ylmethyl] -2H- [1,2,3] triazol-4-yl} amide of 2-methyl-5-phenyloxazole-4-carboxylic acid;

{2- [4- (1,1-difluoroethyl) thiazol-2-ylmethyl] -2H- [1,2,3] triazol-4-yl} amide 5- (3,5-difluorophenyl) -2-methyloxazol- 4-carboxylic acid;

{2- [4- (1,1-difluoroethyl) thiazol-2-ylmethyl] -2H- [1,2,3] triazol-4-yl} amide 2-methyl-5- (3-trifluoromethylphenyl) oxazol-4 β-carboxylic acid;

5- (3-Chlorophenyl) oxazole-4-carboxylic acid {2- [5- (1,1-difluoroethyl) furan-2-ylmethyl] -2H- [1,2,3] triazol-4-yl} amide;

5- (3-Methoxyphenyl) oxazole-4-carboxylic acid {2- [4- (1,1-difluoroethyl) thiazol-2-ylmethyl] -2H- [1,2,3] triazol-4-yl} amide;

{2- [4- (1,1-Difluoroethyl) thiazol-2-ylmethyl] -2H- [1,2,3] triazol-4-yl} amide 2-cyclopropyl-5-phenyloxazole-4-carboxylic acid;

{2- [4- (1,1-Difluoroethyl) thiazol-2-ylmethyl] -2H- [1,2,3] triazol-4-yl} amide 2-methyl-5-phenyloxazole-4-carboxylic acid;

5- (3-Fluorophenyl) oxazole-4-carboxylic acid {2- [5- (1,1-difluoroethyl) furan-2-ylmethyl] -2H- [1,2,3] triazol-4-yl} amide;

5- (3-Chlorophenyl) oxazole-4-carboxylic acid {2- [4- (1,1-difluoroethyl) thiazol-2-ylmethyl] -2H- [1,2,3] triazol-4-yl} amide;

{2- [4- (1,1-difluoroethyl) thiazol-2-ylmethyl] -2H- [1,2,3] triazol-4-yl} amide 5- (3-fluoro-5-methylphenyl) -2- methyloxazole-4-carboxylic acid;

{2- [4- (1,1-difluoroethyl) thiazol-2-ylmethyl] -2H- [1,2,3] triazol-4-yl} amide 2-methyl-5- (3-trifluoromethoxyphenyl) oxazol-4 β-carboxylic acid;

{2- [5- (1,1-Difluoroethyl) furan-2-ylmethyl] -2H- [1,2,3] triazol-4-yl} amide 5- (3-chlorophenyl) -2-methyloxazol-4- carboxylic acid;

5- (4-Fluorophenyl) oxazole-4-carboxylic acid {2- [5- (1,1-difluoroethyl) furan-2-ylmethyl] -2H- [1,2,3] triazol-4-yl} amide;

5-m-tolyloxazole-4-carboxylic acid {2- [4- (1,1-difluoroethyl) thiazol-2-ylmethyl] -2H- [1,2,3] triazol-4-yl} amide;

{2- [5- (1,1-Difluoroethyl) furan-2-ylmethyl] -2H- [1,2,3] triazol-4-yl} amide 5- (3,5-difluorophenyl) -2-methyloxazole- 4-carboxylic acid;

5- (3-Dimethylaminophenyl) oxazole-4-carboxylic acid {2- [5- (1,1-difluoroethyl) furan-2-ylmethyl] -2H- [1,2,3] triazol-4-yl} amide;

5- (3 Fluorophenyl) oxazole-4-carboxylic acid {2- [4- (1,1-difluoroethyl) thiazol-2-ylmethyl] -2H- [1,2,3] triazol-4-yl} amide;

5- (3-Methoxyphenyl) oxazole-4-carboxylic acid {2- [5- (1,1-difluoroethyl) furan-2-ylmethyl] -2H- [1,2,3] triazol-4-yl} amide;

5- (3-Dimethylaminophenyl) oxazole-4-carboxylic acid {2- [4- (1,1-difluoroethyl) thiazol-2-ylmethyl] -2H- [1,2,3] triazol-4-yl} amide;

5-m-tolyloxazole-4-carboxylic acid {2- [5- (1,1-difluoroethyl) furan-2-ylmethyl] -2H- [1,2,3] triazol-4-yl} amide;

{2- [5- (1,1-Difluoroethyl) furan-2-ylmethyl] -2H- [1,2,3] triazol-4-yl} amide 2-methyl-5- (3-trifluoromethylphenyl) oxazol-4 β-carboxylic acid;

5- (4-Fluorophenyl) oxazole-4-carboxylic acid {2- [4- (1,1-difluoroethyl) thiazol-2-ylmethyl] -2H- [1,2,3] triazol-4-yl} amide;

{2- [5- (1,1-Difluoroethyl) furan-2-ylmethyl] -2H- [1,2,3] triazol-4-yl} amide 5- (3-fluoro-5-methylphenyl) -2- methyloxazole-4-carboxylic acid;

{2- [5- (1,1-Difluoroethyl) furan-2-ylmethyl] -2H- [1,2,3] triazol-4-yl} amide 2-methyl-5- (3-trifluoromethoxyphenyl) oxazol-4 β-carboxylic acid;

5-phenyloxazole-4-carboxylic acid {2- [5- (1,1-difluoroethyl) furan-2-ylmethyl] -2H- [1,2,3] triazol-4-yl} amide;

{2- [4- (1,1-difluoroethyl) thiazol-2-ylmethyl] -2H- [1,2,3] triazol-4-yl} amide 5- (3-chlorophenyl) -2-methyloxazol-4- carboxylic acid;

{2- [4- (1,1-Difluoroethyl) thiazol-2-ylmethyl] -2H- [1,2,3] triazol-4-yl} amide of 2-ethyl-5-phenyloxazole-4-carboxylic acid; and

{2- [4- (1,1-Difluoroethyl) oxazol-2-ylmethyl] -2H- [1,2,3] triazol-4-yl} amide 2-methyl-5-m-tolyloxazole-4-carboxylic acid ;

or salts of such compounds.

18. The compound of formula (I) according to claim 1, selected from the group including:

N- (2 - ((2- (1,1-difluoroethyl) oxazol-4-yl) methyl) -2H- [1,2,3] -triazol-4-yl) -2-methyl-5- (m -tolyl) oxazole-4-carboxamide;

{2- [4- (1,1-Difluoroethyl) oxazol-2-ylmethyl] -2H- [1,2,3] triazol-4-yl} amide of 2-methyl-5-phenyloxazole-4-carboxylic acid;

5- (3-Dimethylaminophenyl) oxazole-4-carboxylic acid {2- [4- (1,1-difluoroethyl) oxazol-2-ylmethyl] -2H- [1,2,3] triazol-4-yl} amide;

{2- [4- (1,1-difluoroethyl) oxazol-2-ylmethyl] -2H- [1,2,3] triazol-4-yl} amide 5- (3-dimethylamino-4-fluorophenyl) oxazol-4 β-carboxylic acid; and

{2- [4- (1,1-difluoroethyl) oxazol-2-ylmethyl] -2H- [1,2,3] triazol-4-yl} amide 5- (3-dimethylamino-4-fluorophenyl) -2- methyloxazole-4-carboxylic acid;

or salts of such compounds.

19. The compound of formula (I) according to claim 1 or its pharmaceutically acceptable salt as a medicine.

20. A pharmaceutical composition comprising, as an active component, a compound of formula (I) according to claim 1-18, or a pharmaceutically acceptable salt thereof, and at least one therapeutically inert excipient.

21. The use of the compounds of formula (I) according to claims 1-18, or a pharmaceutically acceptable salt thereof, for the preparation of a medicament for the prevention or treatment of a disease selected from inflammatory diseases, obstructive respiratory diseases, allergic conditions, HIV-mediated retroviral infections, cardio vascular diseases, neuroinflammation, neurological disorders, pain, prion-mediated diseases and amyloid-mediated diseases; and to modulate immune responses.

22. The compound of formula (I) according to claim 1, or a pharmaceutically acceptable salt thereof for the prophylaxis or treatment of a disease selected from inflammatory diseases, obstructive respiratory diseases, allergic conditions, HIV-mediated retroviral infections, cardiovascular diseases, neuroinflammation, neurological disorders, pain, prion-mediated diseases and amyloid-mediated diseases; and to modulate immune responses.