Amide compound and medicinal use thereof

1. A compound of formula [III]:

wherein

R a is

(1) C 5-12 alkyl group which may be substituted with the same or different 1 to 5 substituents selected from Group A, or

wherein

Y a is

(i) single bond, or

(ii) C 1-6 alkylene group, and

cyclic moiety U is

(i) C 3-7 cycloalkyl group which may be substituted with the same or different 1 to 5 substituents selected from Group A,

(ii) C 5-11 spirocyclic cycloalkyl group which may be substituted with the same or different 1 to 5 substituents selected from Group A, or

(iii) C 6-10 aryl group which may be substituted with the same or different 1 to 5 substituents selected from Group A;

R b is a group selected from the following (1) to (3):

(1) C 1-3 alkyl group which may be substituted with the same or different 1 to 5 substituents selected from Group A,

(2) C 2-3 alkenyl group which may be substituted with the same or different 1 to 5 substituents selected from Group A,

(3) C 3-7 cycloalkyl group which may be substituted with the same or different 1 to 5 substituents selected from Group A;

R c is

(1) hydrogen atom, or

(2) C 1-6 alkyl group;

Y c is a C 1-6 alkylene group which may be substituted with the same or different 1 to 5 substituents selected from Group A,

R d1 , R d2 , R d3 , R d4 , and R d5 are the same or different group selected from the following (1) to (7):

(1) hydrogen atom

(2) halogen atom,

(3) C 1-6 alkyl group which may be substituted with the same or different 1 to 5 substituents selected from Group A,

(4) —OR d10 wherein R d10 is hydrogen atom or C 1-6 alkyl group which may be substituted with the same or different 1 to 5 substituents selected from Group A,

(5) —COOR d11 wherein R d11 is hydrogen atom or C 1-6 alkyl group,

(6) C 3-7 cycloalkyl group which may be substituted with the same or different 1 to 5 substituents selected from Group A,

(7) cyano group, or

alternatively R d1 and R d2 , or R d2 and R d3 can be taken together to form a C 6-10 aryl ring fused to the benzene ring to which they are all attached wherein the C 6-10 aryl ring may be substituted with the same or different 1 to 4 substituents selected from Group A; and

Group A is

(a) C 1-6 alkyl group,

(b) halogen atom, and

(c) —OR A1 wherein R A1 is hydrogen atom or C 1-6 alkyl group,

or a pharmaceutically acceptable salt thereof.

2. The compound according to claim 1 , wherein the compound is of formula [IV]:

wherein R a1 is C 1-6 alkyl group,

or a pharmaceutically acceptable salt thereof.

3. The compound according to claim 1 , which is selected from the group consisting of the following formulas or a pharmaceutically acceptable salt thereof:

4. The compound according to claim 1 , which is

or a pharmaceutically acceptable salt thereof.

5. The compound according to claim 1 , which is

or a pharmaceutically acceptable salt thereof.

6. The compound according to claim 1 , which is

or a pharmaceutically acceptable salt thereof.

7. The compound according to claim 1 , which is

or a pharmaceutically acceptable salt thereof.

8. The compound according to claim 1 , which is

9. The compound according to claim 1 , which is

10. The compound according to claim 1 , which is

11. The compound according to claim 1 , which is

12. The compound according to claim 1 , which is

13. The compound according to claim 2 , wherein the compound is of formula [IV-D1]:

or a pharmaceutically acceptable salt thereof.

14. The compound according to claim 2 , wherein the compound is of formula [IV-D2]:

or a pharmaceutically acceptable salt thereof.

15. The compound according to claim 2 , wherein the compound is of formula [IV-D3]:

or a pharmaceutically acceptable salt thereof.

16. The compound according to claim 2 , wherein the compound is of formula [IV-D4]:

or a pharmaceutically acceptable salt thereof.

17. The compound according to any one of claims 1 , 2 , and 13 - 16 , wherein:

R b is C 3-7 cycloalkyl group which may be substituted with the same or different 1 to 5 substituents selected from Group A,

or a pharmaceutically acceptable salt thereof.

18. The compound according to any one of claims 1 , 2 , and 13 - 16 , wherein:

R b is cyclopropyl group,

or a pharmaceutically acceptable salt thereof.

19. The compound according to any one of claims 1 , 2 , and 13 - 16 , wherein:

the cyclic moiety U is C 3-7 cycloalkyl group which may be substituted with the same or different 1 to 5 substituents selected from Group A,

or a pharmaceutically acceptable salt thereof.

20. The compound according to any one of claims 1 , 2 , and 13 - 16 , wherein:

the cyclic moiety U is cyclobutyl group which may be substituted with the same or different 1 to 5 substituents selected from Group A,

or a pharmaceutically acceptable salt thereof.

21. A pharmaceutical composition comprising (a) the compound according to any one of claims 1 and 4 - 7 or a pharmaceutically acceptable salt thereof and (b) a pharmaceutically acceptable carrier.

22. A pharmaceutical composition comprising (a) the compound according to any one of claims 8 - 12 and (b) a pharmaceutically acceptable carrier.

23. A method of inhibiting RORγ in a mammal, comprising administering to said mammal a therapeutically effective amount of the compound according to any one of claims 1 and 4 - 7 or a pharmaceutically acceptable salt thereof, thereby inhibiting RORγ in said mammal.

24. A method of treating an allergic disease, dry eye, or fibrosis in a mammal, comprising administering to said mammal a therapeutically effective amount of the compound according to any one of claims 1 and 4 - 7 or a pharmaceutically acceptable salt thereof, thereby treating the allergic disease, dry eye, or fibrosis in said mammal.

25. A method of treating rheumatoid arthritis, psoriasis, inflammatory bowel disease, multiple sclerosis, systemic lupus erythematosus, ankylosing spondylitis, uveitis, polymyalgia rheumatica, or type I diabetes in a mammal, comprising administering to said mammal a therapeutically effective amount of the compound according to any one of claims 1 and 4 - 7 or a pharmaceutically acceptable salt thereof, thereby treating the rheumatoid arthritis, psoriasis, inflammatory bowel disease, multiple sclerosis, systemic lupus erythematosus, ankylosing spondylitis, uveitis, polymyalgia rheumatica, or type I diabetes in said mammal.

26. The method according to claim 25 , wherein the autoimmune disease is selected from the group consisting of rheumatoid arthritis, psoriasis, inflammatory bowel disease, multiple sclerosis, systemic lupus erythematosus, ankylosing spondylitis, uveitis, polymyalgia rheumatica, and type I diabetes.

27. The method according to claim 25 , wherein the inflammatory bowel disease is Crohn's disease or ulcerative colitis.

28. A method of treating an allergic disease in a mammal, comprising administering to said mammal a therapeutically effective amount of the compound according to any one of claims 1 and 4 - 7 or a pharmaceutically acceptable salt thereof, thereby treating the allergic disease in said mammal.

29. The method according to claim 28 , wherein the allergic disease is asthma.

30. A method of treating dry eye in a mammal, comprising administering to said mammal a therapeutically effective amount of the compound according to any one of claims 1 and 4 - 7 or a pharmaceutically acceptable salt thereof, thereby treating dry eye in said mammal.

31. A method of treating fibrosis in a mammal, comprising administering to said mammal a therapeutically effective amount of the compound according to any one of claims 1 and 4 - 7 or a pharmaceutically acceptable salt thereof, thereby treating fibrosis in said mammal.

32. The method according to claim 31 , wherein the fibrosis is pulmonary fibrosis or primary biliary cirrhosis.

33. A method of treating diabetes in a mammal, comprising administering to said mammal a therapeutically effective amount of the compound according to any one of claims 1 and 4 - 7 or a pharmaceutically acceptable salt thereof, thereby treating diabetes in said mammal.

34. The method according to claim 33 , wherein the metabolic disease is diabetes.

35. The method according to claim 33 , wherein the diabetes is type I diabetes.

36. The method according to claim 33 , wherein the diabetes is type II diabetes.

37. A method of inhibiting RORγ in a mammal, comprising administering to said mammal a therapeutically effective amount of the compound according to any one of claims 8 - 12 , thereby inhibiting RORγ in said mammal.

38. A method of treating an allergic disease, dry eye, or fibrosis in a mammal, comprising administering to said mammal a therapeutically effective amount of the compound according to any one of claims 8 - 12 , thereby treating the allergic disease, dry eye, or fibrosis in said mammal.

39. A method of treating rheumatoid arthritis, psoriasis, inflammatory bowel disease, multiple sclerosis, systemic lupus erythematosus, ankylosing spondylitis, uveitis, polymyalgia rheumatica, or type I diabetes in a mammal, comprising administering to said mammal a therapeutically effective amount of the compound according to any one of claims 8 - 12 , thereby treating the rheumatoid arthritis, psoriasis, inflammatory bowel disease, multiple sclerosis, systemic lupus erythematosus, ankylosing spondylitis, uveitis, polymyalgia rheumatica, or type I diabetes in said mammal.

40. The method according to claim 39 , wherein the autoimmune disease is selected from the group consisting of rheumatoid arthritis, psoriasis, inflammatory bowel disease, multiple sclerosis, systemic lupus erythematosus, ankylosing spondylitis, uveitis, polymyalgia rheumatica, and type I diabetes.

41. The method according to claim 39 , wherein the inflammatory bowel disease is Crohn's disease or ulcerative colitis.

42. A method of treating an allergic disease in a mammal, comprising administering to said mammal a therapeutically effective amount of the compound according to any one of claims 8 - 12 , thereby treating the allergic disease in said mammal.

43. The method according to claim 42 , wherein the allergic disease is asthma.

44. A method of treating dry eye in a mammal, comprising administering to said mammal a therapeutically effective amount of the compound according to any one of claims 8 - 12 , thereby treating dry eye in said mammal.

45. A method of treating fibrosis in a mammal, comprising administering to said mammal a therapeutically effective amount of the compound according to any one of claims 8 - 12 , thereby treating fibrosis in said mammal.

46. The method according to claim 45 , wherein the fibrosis is pulmonary fibrosis or primary biliary cirrhosis.

47. A method of treating diabetes in a mammal, comprising administering to said mammal a therapeutically effective amount of the compound according to any one of claims 8 - 12 , thereby treating diabetes in said mammal.

48. The method according to claim 47 , wherein the metabolic disease is diabetes.

49. The method according to claim 47 , wherein the diabetes is type I diabetes.

50. The method according to claim 47 , wherein the diabetes is type II diabetes.