Heterocyclic compound

Patent metadata

Field	Value
Publication number	US-10544111-B2
Application number	US-201816230634-A
Country	US
Kind code	B2
Filing date	Dec 21, 2018
Priority date	Oct 24, 2014
Publication date	Jan 28, 2020
Grant date	Jan 28, 2020

Abstract

Provided is a heterocyclic compound having a superior RBP4-lowering action and useful as a medicament for the prophylaxis or treatment of a disease or symptom mediated by an increase in RBP4 or retinol supplied by RBP4.
A compound represented by the formula (I):

wherein each symbol is as defined in the Description, or a salt thereof has a superior RBP4-lowering action, and is useful as a medicament for the prophylaxis or treatment of a disease or symptom mediated by an increase in RBP4 or retinol supplied by RBP4.

First claim

The invention claimed is:

1. A method for treating an ophthalmic disease in a mammal, comprising administering to a mammal a medicament comprising an effective amount of the compound represented by the formula (I):

wherein
ring A is a pyrazole ring, a pyridine ring, or a pyrimidine ring;
X is CH 2 or O; and
R is a hydrogen atom or a C 1-6 alkyl group,
or a salt thereof.

2. The method of claim 1 , wherein the medicament further comprises a pharmacologically acceptable carrier.

3. The method of claim 1 , wherein the ophthalmic disease is selected from the group consisting of dry age-related macular degeneration, wet age-related macular degeneration, geographic atrophy, denaturation of photoreceptors, macular dystrophy, retinal dystrophy, retinopathy, retinitis pigmentosa, retinal vein occlusion, retinal artery obstruction, glaucoma, and Stargardt's disease.

4. The method of claim 2 , wherein the ophthalmic disease is dry age-related macular degeneration.

5. The method of claim 2 , wherein the ophthalmic disease is wet age-related macular degeneration.

6. The method of claim 4 , wherein the compound is ((2-(3,5-bis(Trifluoromethyl)phenyl)-pyrimidin-5-yl)oxy)acetic acid or a salt thereof.

7. The method of claim 4 , wherein the compound is ((6-(3,5-bis(Trifluoromethyl)phenyl)-pyridin-3-yl)oxy)acetic acid or a salt thereof.

8. The method of claim 4 , wherein the compound is 3-(3-(3,5-bis(Trifluoromethyl)phenyl)-1H-pyrazol-1-yl)propanoic acid or a salt thereof.

9. The method of claim 4 , wherein the compound is ((1-(3,5-bis(Trifluoromethyl)phenyl)-1H-pyrazol-3-yl)oxy)acetic acid or a salt thereof.

10. The method of claim 5 , wherein the compound is ((2-(3,5-bis(Trifluoromethyl)phenyl)-pyrimidin-5-yl)oxy)acetic acid or a salt thereof.

11. The method of claim 5 , wherein the compound is ((6-(3,5-bis(Trifluoromethyl)phenyl)-pyridin-3-yl)oxy)acetic acid or a salt thereof.

12. The method of claim 5 , wherein the compound is 3-(3-(3,5-bis(Trifluoromethyl)phenyl)-1H-pyrazol-1-yl)propanoic acid or a salt thereof.

13. The method of claim 5 , wherein the compound is ((1-(3,5-bis(Trifluoromethyl)phenyl)-1H-pyrazol-3-yl)oxy)acetic acid or a salt thereof.

14. The method of claim 2 , wherein the ophthalmic disorder is Stargardt's disease.

15. The method of claim 14 , wherein the compound is ((2-(3,5-bis(Trifluoromethyl)phenyl)-pyrimidin-5-yl)oxy)acetic acid or a salt thereof.

16. The method of claim 14 , wherein the compound is ((6-(3,5-bis(Trifluoromethyl)phenyl)-pyridin-3-yl)oxy)acetic acid or a salt thereof.

17. The method of claim 14 , wherein the compound is 3-(3-(3,5-bis(Trifluoromethyl)phenyl)-1H-pyrazol-1-yl)propanoic acid or a salt thereof.

18. The method of claim 14 , wherein the compound is ((1-(3,5-bis(Trifluoromethyl)phenyl)-1H-pyrazol-3-yl)oxy)acetic acid or a salt thereof.

19. The method of claim 2 , wherein the ophthalmic disease is retinal dystrophy.

20. The method of claim 19 , wherein the compound is ((2-(3,5-bis(Trifluoromethyl)phenyl)-pyrimidin-5-yl)oxy)acetic acid or a salt thereof.

21. The method of claim 19 , wherein the compound is ((6-(3,5-bis(Trifluoromethyl)phenyl)-pyridin-3-yl)oxy)acetic acid or a salt thereof.

22. The method of claim 19 , wherein the compound is 3-(3-(3,5-bis(Trifluoromethyl)phenyl)-1H-pyrazol-1-yl)propanoic acid or a salt thereof.

23. The method of claim 19 , wherein the compound is ((1-(3,5-bis(Trifluoromethyl)phenyl)-1H-pyrazol-3-yl)oxy)acetic acid or a salt thereof.

24. The method of claim 2 , wherein the ophthalmic disease is retinitis pigmentosa.

25. The method of claim 24 , wherein the compound is ((2-(3,5-bis(Trifluoromethyl)phenyl)-pyrimidin-5-yl)oxy)acetic acid or a salt thereof.

26. The method of claim 24 , wherein the compound is ((6-(3,5-bis(Trifluoromethyl)phenyl)-pyridin-3-yl)oxy)acetic acid or a salt thereof.

27. The method of claim 24 , wherein the compound is 3-(3-(3,5-bis(Trifluoromethyl)phenyl)-1H-pyrazol-1-yl)propanoic acid or a salt thereof.

28. The method of claim 24 , wherein the compound is ((1-(3,5-bis(Trifluoromethyl)phenyl)-1H-pyrazol-3-yl)oxy)acetic acid or a salt thereof.

29. The method of claim 2 , wherein the ophthalmic disorder is geographic atrophy.

30. The method of claim 29 , wherein the compound is ((2-(3,5-bis(Trifluoromethyl)phenyl)-pyrimidin-5-yl)oxy)acetic acid or a salt thereof.

31. The method of claim 29 , wherein the compound is ((6-(3,5-bis(Trifluoromethyl)phenyl)-pyridin-3-yl)oxy)acetic acid or a salt thereof.

32. The method of claim 29 , wherein the compound is 3-(3-(3,5-bis(Trifluoromethyl)phenyl)-1H-pyrazol-1-yl)propanoic acid or a salt thereof.

33. The method of claim 29 , wherein the compound is ((1-(3,5-bis(Trifluoromethyl)phenyl)-1H-pyrazol-3-yl)oxy)acetic acid or a salt thereof.

34. The method of claim 3 wherein the compound is ((2-(3,5-bis(Trifluoromethyl)phenyl) pyrimidin-5-yl)oxy)acetic acid or a salt thereof.

35. The method of claim 34 , wherein the medicament further comprises a pharmacologically acceptable carrier.

36. The method of claim 3 wherein the compound is ((6-(3,5-bis(Trifluoromethyl)phenyl) pyridin-3-yl)oxy)acetic acid or a salt thereof.

37. The method of claim 36 , wherein the medicament further comprises a pharmacologically acceptable carrier.

38. The method of claim 3 wherein the compound is 3-(3-(3,5-bis(Trifluoromethyl)phenyl)-1H-pyrazol-1-yl)propanoic acid or a salt thereof.

39. The method of claim 38 , wherein the medicament further comprises a pharmacologically acceptable carrier.

40. The method of claim 3 wherein the compound is ((1-(3,5-bis(Trifluoromethyl)phenyl)-1H-pyrazol-3-yl)oxy)acetic acid or a salt thereof.

41. The method of claim 40 , wherein the medicament further comprises a pharmacologically acceptable carrier.

Assignees

• Takeda Pharmaceuticals Co

Inventors

• Banno Yoshihiro
• Kamaura Masahiro
• Takami Kazuaki
• Fukuda Koichiro
• Sasaki Shigekazu

Classifications

• C12N15/09

  Recombinant DNA-technology · CPC title

• C07D263/38

  attached in position 2 · CPC title

• A61K31/421

  1,3-Oxazoles, e.g. pemoline, trimethadione · CPC title

• C07D239/34 Primary

  One oxygen atom · CPC title

• C07D213/65

  attached in position 3 or 5 · CPC title