SALTS AND HYDRATES OF SALTS OF N,N'-BIS[2-(1H-IMIDAZOL-4-YL)ETHYL]OXALAMIDE FOR THE TREATMENT OF COUGH AND FIBROSIS OF THE LUNG, LIVER, KIDNEYS, PANCREAS AND HEART

Claims

1. Compound of formula (I) in which A is selected from the group consisting of HCl, H3PO4, maleic acid, malonic acid, fumaric acid, HI, HBr, H2SO4, benzenesulfonic acid, tartaric acid, malic acid, p-toluenesulfonic acid, oxalic acid, glycolic acid, glutaric acid, camphorsulfonic acid, methanesulfonic acid, formic acid, ethanesulfonic acid, mandelic acid, nicotinic acid, succinic acid and adipic acid, n represents 1 or 2, z is a number between 0 and 5.

2. The compound according to claim 1, selected from the group including N,N'-bis[2-(1H-imidazol-4-yl)ethyl]oxalamide dihydrochloride dihydrate of formula 1 N,N'-bis[2-(1H-imidazol-4-yl)ethyl]oxalamide diphosphate of formula 2: (2), N,N'-bis[2-(1H-imidazol-4-yl)ethyl]oxalamide dihydrate dimaleate of formula 3: (3), N,N'-bis[2-(1H-imidazol-4-yl)ethyl]oxalamide dimalonate formula 4: (4), N,N'-bis[2-(1H-imidazol-4-yl)ethyl]oxalamide fumarate formula 5: (5), N,N'-bis[2-(1H-imidazol-4-yl)ethyl]oxalamide dihydrate dihydroiodide of formula 6: N,N'-bis[2-(1H-imidazol-4-yl)ethyl]oxalamide dihydrate dihydrobromide of formula 7: N,N'-bis[2-(1H-imidazol-4-yl)ethyl]oxalamide sulfate trihydrate of formula 8: dibenzenesulfonate N,N'-bis[2-(1H-imidazol-4-yl)ethyl]oxalamide formula 9: L,D-tartrate N,N'-bis[2-(1H-imidazol-4-yl)ethyl]oxalamide formula 10: (10), L-malate N,N'-bis[2-(1H-imidazol-4-yl)ethyl]oxalamide formula 11: (11), Diparatoluenesulfonate N,N'-bis[2-(1H-imidazol-4-yl)ethyl]oxalamide formula 12: (12), oxalate N,N'-bis[2-(1H-imidazol-4-yl)ethyl]oxalamide formula 13: (13), dioxalate N,N'-bis[2-(1H-imidazol-4-yl)ethyl]oxalamide formula 14: (14), Diadipinate N,N'-bis[2-(1H-imidazol-4-yl)ethyl]oxalamide monohydrate of formula 15: N,N'-bis[2-(1H-imidazol-4-yl)ethyl]oxalamide dihydrate dimethanesulfonate of formula 16: N,N'-bis[2-(1H-imidazol-4-yl)ethyl]oxalamide succinate of formula 17: (17) di-D-malate N,N'-bis[2-(1H-imidazol-4-yl)ethyl]oxalamide formula 18: D-Malate N,N'-bis[2-(1H-imidazol-4-yl)ethyl]oxalamide formula 19: N,N'-bis[2-(1H-imidazol-4-yl)ethyl]oxalamide diglycolate formula , N,N'-bis[2-(1H-imidazol-4-yl)ethyl]oxalamide glutarate dihydrate formula , N,N'-bis[2-(1H-imidazol-4-yl)ethyl]oxalamide dicamphorsulfonate formula , N,N'-bis[2-(1H-imidazol-4-yl)ethyl]oxalamide diformate formula , N,N'-bis[2-(1H-imidazol-4-yl)ethyl]oxalamide diethanesulfonate formula , N,N'-bis[2-(1H-imidazol-4-yl)ethyl]oxalamide malonate dihydrate formula , Formula of N,N'-bis[2-(1H-imidazol-4-yl)ethyl]oxalamide dimandelate , Formula of N,N'-bis[2-(1H-imidazol-4-yl)ethyl]oxalamide dinicotinate , N,N'-bis[2-(1H-imidazol-4-yl)ethyl]oxalamide disulfate formula , Formula of N,N'-bis[2-(1H-imidazol-4-yl)ethyl]oxalamide D-tartrate: , Formula of N,N'-bis[2-(1H-imidazol-4-yl)ethyl]oxalamide L-tartrate , N,N'-bis[2-(1H-imidazol-4-yl)ethyl]oxalamide dihydroiodide formula: , and N,N'-bis[2-(1H-imidazol-4-yl)ethyl]oxalamide dihydrobromide formula: На .

3. A crystalline form of N,N'-bis[2-(1H-imidazol-4-yl)ethyl]oxalamide dihydrochloride dihydrate, characterized in that it is characterized by peak positions in the powder X-ray diffraction pattern, 2θ, deg (± 0.2°): 21.7, 23.3 and 24.

2.

4. The crystalline form according to claim 3, characterized by peak positions in the powder X-ray diffraction pattern, 2θ. deg (± 0.2°): 14.6, 21.1, 21.7, 23.3, 24.2, 27.3, 29.0 and 34.

7.

5. The crystalline form of N,N'-bis[2-(1H-imidazol-4-yl)ethyl]oxalamide dihydrochloride dihydrate, characterized by monoclinic syngony, the values ​​of the edges of the crystal cell Å: 5.72 ± 0.50 Å, 24.20 ± 0.50 Å, 6.95 ± 0.50 Å; and the value of the angle (deg): 104.04 o ± 5.00 o .

6. A crystalline form of N,N'-bis[2-(1H-imidazol-4-yl)ethyl]oxalamide diphosphate, characterized in that it is characterized by peak positions in the powder X-ray diffraction pattern, 2θ, deg (± 0.2°): 20.4, 23.3 and 24.

7.

7. The crystalline form according to claim 6, characterized by peak positions in the powder X-ray diffraction pattern, 2θ, deg (± 0.2°): 6.5, 12.5, 20.2, 20.4, 23.3, 23.4, 23.8 and 24.

7.

8. Crystalline N,N'-bis[2-(1H-imidazol-4-yl)ethyl]oxalamide diphosphate is characterized by triclinic syngony, the values ​​of the edges of the crystal cell, Å: 4.90 ± 0.50 Å, 7.43 ± 0.50 Å, 14.02 ± 0.50 Å; and the values ​​of the angles (deg): 103.84 o ± 5.00 o , 94.02 o ± 5.00 o , 97.90 o ± 5.00 o .

9. A crystalline form of N,N'-bis[2-(1H-imidazol-4-yl)ethyl]oxalamide dimaleate dihydrate, characterized in that it is characterized by peak positions in the powder X-ray diffraction pattern, 2θ, deg (± 0.2°): 9.3, 21.2 and 25.

4.

10. The crystalline form according to claim 9, characterized by peak positions in the powder X-ray diffraction pattern, 2θ, deg (± 0.2°): 9.3, 18.4, 18.6, 21.2, 22.2, 25.1, 25.4 and 29.

9.

11. The crystalline form of N,N'-bis[2-(1H-imidazol-4-yl)ethyl]oxalamide dimaleate dihydrate, characterized by triclinic syngony, the values ​​of the edges of the crystal cell, Å: 4.97 ± 0.50 Å, 10.32 ± 0.50 Å, 13.53 ± 0.50 Å; and the values ​​of the angles (deg): 109.72 o ± 5.00 o , 96.62 o ± 5.00 o , 98.80 o ± 5.00 o .

12. Crystalline form of N,N'-bis[2-(1H-imidazol-4-yl)ethyl]oxalamide dimalonate, characterized by peak positions in powder X-ray diffraction pattern, 2θ, deg (± 0.2°): 6.5, 23.3 and 31.

1.

13. The crystalline form according to claim 12, characterized by peak positions in the powder X-ray diffraction pattern, 2θ, deg (± 0.2°): 6.5, 13.9, 19.7, 23.3, 23.5, 25.5, 26.2, 31.1 and 37.

3.

14. The crystalline form of N,N'-bis[2-(1H-imidazol-4-yl)ethyl]oxalamide dimalonate, characterized by triclinic syngony, the values ​​of the edges of the crystal cell, Å: 4.59 ± 0.50 Å, 8.53 ± 0.50 Å, 14.01 ± 0.50 Å; and the values ​​of the angles (deg): 103.91 o ± 5.00 o , 92.18 o ± 5.00 o , 96.82 o ± 5.00 o .

15. Crystalline form of N,N'-bis[2-(1H-imidazol-4-yl)ethyl]oxalamide fumarate, characterized by peak positions in powder X-ray diffraction pattern, 2θ, deg (± 0.2°): 21.3, 23.6 and 27.

5.

16. The crystalline form according to claim 15, characterized by peak positions in the powder X-ray diffraction pattern, 2θ, deg (± 0.2°): 16.5, 18.8, 18.9, 2.3, 21.4, 22.0, 22.5, 23.6, 24.3, 27.5, 28.1 and 28.

6.

17. The crystalline form of N,N'-bis[2-(1H-imidazol-4-yl)ethyl]oxalamide fumarate, characterized by monoclinic syngony, the values ​​of the edges of the crystal cell, Å: 12.87 ± 0.50 Å, 5.10 ± 0.50 Å, 14.45 ± 0.50 Å; and the values ​​of the angles (deg): 104.36 o ± 5.00 o .

18. A crystalline form of N,N'-bis[2-(1H-imidazol-4-yl)ethyl]oxalamide dihydroiodide dihydrate, characterized by peak positions in the powder X-ray diffraction pattern, 2θ, deg (± 0.2°): 20.4, 22.6 and 26.

2.

19. The crystalline form according to claim 18, characterized by peak positions in the powder X-ray diffraction pattern, 2θ, deg (± 0.2°): 18.2, 20.4, 22.6, 23.6, 26.2, 31.3, 33.3 and 36.

5.

20. The crystalline form of N,N'-bis[2-(1H-imidazol-4-yl)ethyl]oxalamide dihydroiodide dihydrate, characterized by triclinic syngony, the values ​​of the edges of the crystal cell, Å: 7.76 ± 0.50 Å, 8.04 ± 0.50 Å, 8.99 ± 0.50 Å; and the values ​​of the angles (deg): 88.05 o ± 5.00 o , 74.66 o ± 5.00o , 70.66 o ± 5.00 o .

21. A crystalline form of N,N'-bis[2-(1H-imidazol-4-yl)ethyl]oxalamide dihydrobromide dihydrate, characterized by peak positions in the powder X-ray diffraction pattern, 2θ, deg (± 0.2°): 22.0, 22.8, and 25.

0.

22. The crystalline form according to claim 21, characterized by peak positions in the powder X-ray diffraction pattern, 2θ, deg (± 0.2°): 12.0, 20.5, 21.2, 22.0, 22.8, 23.2, 23.7, 24.3, 25.0, 26.8 and 31.

8.

23. The crystalline form of N,N'-bis[2-(1H-imidazol-4-yl)ethyl]oxalamide dihydrobromide dihydrate, characterized by triclinic syngony, the values ​​of the edges of the crystal cell, Å: 5.11 ± 0.50 Å, 7.80 ± 0.50 Å, 12.65 ± 0.50 Å; and the values ​​of the angles (deg): 104.78 o ± 5.00 o , 96.31 o ± 5.00 o , 100.38 o ± 5.00 o .

24. A crystalline form of N,N'-bis[2-(1H-imidazol-4-yl)ethyl]oxalamide sulfate trihydrate, characterized by peak positions in the powder X-ray diffraction pattern, 2θ, deg (± 0.2°): 6.6, 21.3, 24.

5.

25. The crystalline form according to claim 23, characterized by peak positions in the powder X-ray diffraction pattern, 2θ, deg (± 0.2°): 6.3, 6.6, 11.9, 13.2, 15.9, 18.2, 21.1, 21.3, 22.9, 23.6, 24.5, 26.0 and 27.

4.

26. The crystalline form of N,N'-bis[2-(1H-imidazol-4-yl)ethyl]oxalamide sulfate trihydrate, characterized by monoclinic syngony, the values ​​of the edges of the crystal cell, Å: 8.22 ± 0.50 Å, 8.77 ± 0.50 Å, 27.13 ± 0.50 Å; and the values ​​of the angles (deg): 97.61 o ± 5.00 o .

27. A crystalline form of N,N'-bis[2-(1H-imidazol-4-yl)ethyl]oxalamide dibenzenesulfonate, characterized by peak positions in the powder X-ray diffraction pattern, 2θ, deg (± 0.2°): 20.9, 21.6, and 22.

4.

28. The crystalline form according to claim 27, characterized by peak positions in the powder X-ray diffraction pattern, 2θ, deg (± 0.2°): 13.3, 16.2, 17.9, 18.8, 20.9, 21.6, 22.4, 22.6, 25.0, 25.1 and 26.

6.

29. The crystalline form of N,N'-bis[2-(1H-imidazol-4-yl)ethyl]oxalamide dibenzenesulfonate, characterized by monoclinic syngony, the values ​​of the edges of the crystal cell, Å: 9.61 ± 0.50 Å, 10.74 ± 0.50 Å, 12.99 ± 0.50 Å; and the values ​​of the angles (deg): 101.92 o ± 5.00 o .

30. A crystalline form of N,N'-bis[2-(1H-imidazol-4-yl)ethyl]oxalamide tartrate, characterized by peak positions in the powder X-ray diffraction pattern, 2θ, deg (± 0.2°): 6.9, 19.9, and 23.

6.

31. The crystalline form according to claim 30, characterized by peak positions in the powder X-ray diffraction pattern, 2θ, deg (± 0.2°): 6.9, 10.8, 18.4, 19.9, 21.1, 21.5 and 27.

2.

32. The crystalline form of N,N'-bis[2-(1H-imidazol-4-yl)ethyl]oxalamide L, D-tartrate, characterized by triclinic syngony, the values ​​of the edges of the crystal cell, Å: 9.00 ± 0.50 Å, 9.16 ± 0.50 Å, 13.54 ± 0.50 Å; and the values ​​of the angles (deg): 108.59 o ± 5.00 o , 91.87 o ± 5.00 o , 112.10 o ± 5.00 o .

33. A crystalline form of N,N'-bis[2-(1H-imidazol-4-yl)ethyl]oxalamide L-malate characterized by peak positions in the powder X-ray diffraction pattern, 2θ, deg (± 0.2°): 19.3, 24.0, and 25.

3.

34. The crystalline form according to claim 33, characterized by peak positions in the powder X-ray diffraction pattern, 2θ, deg (± 0.2°): 7.0, 11.5, 17.1, 19.3, 21.4, 23.9, 24.8, 25.32 and 32.

6.

35. The crystalline form of N,N'-bis[2-(1H-imidazol-4-yl)ethyl]oxalamide L-malate, characterized by triclinic syngony, the values ​​of the edges of the crystal cell, Å: 4.68 ± 0.50 Å, 7.81 ± 0.50 Å, 12.74 ± 0.50 Å; and the values ​​of the angles (deg): 81.64 ± 5.00 o , 81.79 o ± 5.00 o , 80.66 o ± 5.00 o .

36. A crystalline form of N,N'-bis[2-(1H-imidazol-4-yl)ethyl]oxalamide diparatoluenesulfonate, characterized by peak positions in the powder X-ray diffraction pattern, 2θ, deg (± 0.2°): 7.4, 15.7, and 23.

1.

37. The crystalline form according to claim 36, characterized by peak positions in the powder X-ray diffraction pattern, 2θ, deg (± 0.2°): 7.4, 12.3, 13.2, 15.0, 15.7, 18.4, 18.5, 21.4, 22.3, 23.1, 24.6, 25.4, 25.7, 25.9, 26.7, 27.0, 27.6, 28.2, 30.2, 32.2 and 33.

3.

38. The crystalline form of N,N'-bis[2-(1H-imidazol-4-yl)ethyl]oxalamide diparatoluenesulfonate, characterized by monoclinic syngony, the values ​​of the edges of the crystal cell, Å: 7.25 ± 0.50 Å, 8.06 ± 0.50 Å, 23.86 ± 0.50 Å; and the values ​​of the angles (deg): 95.81 o ± 5.00 o .

39. Crystalline form of N,N'-bis[2-(1H-imidazol-4-yl)ethyl]oxalamide oxalate, characterized by peak positions in powder X-ray diffraction pattern, 2θ, deg (± 0.2°): 16.5, 16.6, 18.

7.

40. The crystalline form according to claim 39, characterized by peak positions in the powder X-ray diffraction pattern, 2θ, deg (± 0.2°): 10.4, 16.5, 16.6, 18.7, 20.8, 22.0, 25.1, 25.3, 26.4, 33.6 and 43.

2.

41. The crystalline form of N,N'-bis[2-(1H-imidazol-4-yl)ethyl]oxalamide oxalate, characterized by monoclinic syngony, the values ​​of the edges of the crystal cell, Å: 14.91 ± 0.50 Å, 21.31 ± 0.50 Å, 22.43 ± 0.50 Å; and the values ​​of the angles (deg): 22.43 o ± 5.00 o .

42. Crystalline form of N,N'-bis[2-(1H-imidazol-4-yl)ethyl]oxalamide dioxalate, characterized by peak positions in powder X-ray diffraction pattern, 2θ, deg (± 0.2°): 24.1, 25.4, 27.

5.

43. The crystalline form according to claim 42, characterized by peak positions in the powder X-ray diffraction pattern, 2θ, deg (± 0.2°): 19.3, 22.4, 24.1, 25.4, 27.5 and 30.

0.

44. The crystalline form of N,N'-bis[2-(1H-imidazol-4-yl)ethyl]oxalamide dioxalate, characterized by monoclinic syngony, the values ​​of the edges of the crystal cell, Å: 10.84 ± 0.50 Å, 5.64 ± 0.50 Å, 16.10 ± 0.50 Å; and the values ​​of the angles (deg): 100.51 o ± 5.00 o .

45. A crystalline form of N,N'-bis[2-(1H-imidazol-4-yl)ethyl]oxalamide diadipate monohydrate, characterized by peak positions in the powder X-ray diffraction pattern, 2θ, deg (± 0.2°): 19.5, 23.7, and 25.

8.

46. ​​The crystalline form according to claim 45, characterized by peak positions in the powder X-ray diffraction pattern (± 0.2°): 14.1, 18.9, 19.5, 20.9, 22.7, 23.7, 25.8 and 36.

2.

47. The crystalline form of N,N'-bis[2-(1H-imidazol-4-yl)ethyl]oxalamide diadipinate monohydrate, characterized by monoclinic syngony, the values ​​of the edges of the crystal cell, Å: 4.99 ± 0.50 Å, 7.92 ± 0.50 Å, 18.33 ± 0.50 Å; and the values ​​of the angles (deg): 82.98 o ± 5.00 o , 88.26 o ± 5.00 o and 77.81 o ± 5.00 o .

48. A crystalline form of N,N'-bis[2-(1H-imidazol-4-yl)ethyl]oxalamide dimethanesulfonate dihydrate, characterized by peak positions in the powder X-ray diffraction pattern, 2θ, deg (± 0.2°): 6.4, 23.9, and 22.

5.

49. The crystalline form according to claim 48, characterized by peak positions in the powder X-ray diffraction pattern, 2θ, deg (± 0.2°): 6.4, 12.8, 19.0, 19.3, 22.3, 22.5, 22.9, 23.1, 23.9, 25.8 and 33.

1.

50. The crystalline form of N,N'-bis[2-(1H-imidazol-4-yl)ethyl]oxalamide dimethanesulfonate dihydrate, characterized by monoclinic syngony, the values ​​of the edges of the crystal cell, Å: 5.85 ± 0.50 Å, 7.19 ± 0.50 Å, 14.02 ± 0.50 Å; and the values ​​of the angles (deg): 97.43 o ± 5.00 o , 98.30 o ± 5.00 o and 102.48 o ± 5.00 o .

51. A crystalline form of N,N'-bis[2-(1H-imidazol-4-yl)ethyl]oxalamide succinate, characterized by peak positions in the powder X-ray diffraction pattern, 2θ, deg (± 0.2°): 6.2, 21.2, and 26.

3.

52. The crystalline form according to claim 51, characterized by the positions of the peaks in the powder X-ray diffraction pattern, 2θ, deg (± 0.2°): 6.2, 16.9, 18.4, 18.6, 19.4, 20.4, 21.2, 26.3, 24.4, 25.

6.

53. The crystalline form of N,N'-bis[2-(1H-imidazol-4-yl)ethyl]oxalamide succinate, characterized by monoclinic syngony, the values ​​of the edges of the crystal cell, Å: 13.02 ± 0.50 Å, 5.08 ± 0.50 Å, 14.51 ± 0.50 Å; and the values ​​of the angles (deg): 104.87 o ± 5.00 o .

54. A crystalline form of N,N'-bis[2-(1H-imidazol-4-yl)ethyl]oxalamide di-D-malate, characterized by peak positions in the powder X-ray diffraction pattern, 2θ, deg (± 0.2°): 22.1, 22.9, and 23.

6.

55. The crystalline form according to claim 54, characterized by peak positions in the powder X-ray diffraction pattern, 2θ, deg (± 0.2°): 5.9, 15.7, 19.5, 20.3, 21.4, 22.1, 22.9, 23.3, 23.6, 24.4, 28.0 and 32.

3.

56. The crystalline form of N,N'-bis[2-(1H-imidazol-4-yl)ethyl]oxalamide di-D-malate, characterized by monoclinic syngony, the values ​​of the edges of the crystal cell, Å: 5.03 ± 0.50 Å, 7.83 ± 0.50 Å, 15.05 ± 0.50 Å; and the values ​​of the angles (deg): 83.89 ± 5.00 o , 84.35 o ± 5.00 o, 78.31 o ± 5.00 o .

57. A crystalline form of N,N'-bis[2-(1H-imidazol-4-yl)ethyl]oxalamide D-malate, characterized by peak positions in the powder X-ray diffraction pattern, 2θ, deg (± 0.2°): 19.4, 23.5 and 24.

1.

58. The crystalline form according to claim 57, characterized by peak positions in the powder X-ray diffraction pattern, 2θ, deg (± 0.2°): 17.1, 19.4, 21.5, 22.1, 23.0, 23.3, 23.5, 24.1, 24.8, 25.4 and 28.

5.

59. The crystalline form of N,N'-bis[2-(1H-imidazol-4-yl)ethyl]oxalamide D-malate, characterized by monoclinic syngony, the values ​​of the edges of the crystal cell, Å: 9.54 ± 0.50 Å, 11.86 ± 0.50 Å, 16.02 ± 0.50 Å; and the values ​​of the angles (deg): 101.01 o ± 5.

00.

60. A method for obtaining a crystalline form of a compound of formula (I) according to paragraphs 1-59, comprising the following steps: a) providing N,N'-bis[2-(1H-imidazol-4-yl)ethyl]oxalamide b) providing a solution of acid in water and / or an organic solvent and / or a mixture of solvents; c) mixing the components obtained in steps a) and b) to obtain a solution of N,N'-bis[2-(1H-imidazol-4-yl)ethyl]oxalamide salt; d) crystallization of the obtained salt by diluting the reaction mixture with an organic solvent; e) isolating the resulting salt by removing the solvent from the reaction mixture in a vacuum, dissolving the residue in isopropanol and maintaining the resulting solution at +5°C until the salt crystals precipitate; f) separation of salt crystals from the solvent.

61. A method for obtaining a crystalline form of a compound of formula (I) according to paragraphs 1-59, comprising the following steps: a) providing N,N'-bis[2-(1H-imidazol-4-yl)ethyl]oxalamide; b) providing a solution of acid in water and / or an organic solvent and / or a mixture of solvents; c) mixing the components obtained in steps a) and b) to obtain a solution of N,N'-bis[2-(1H-imidazol-4-yl)ethyl]oxalamide salt; e) isolation of the obtained salt by crystallization from water; f) separation of salt crystals from water.

62. The method according to claim 60 or 61, wherein the acid solvent in step (b) is water.

63. The method according to any one of claims 60-62, wherein N,N'-bis[2-(1H-imidazol-4-yl)ethyl]oxalamide in step (a) is provided in the form of a solid.

64. The method according to any one of claims 60-62, wherein N,N'-bis[2-(1H-imidazol-4-yl)ethyl]oxalamide in step (a) is provided in the form of a suspension or solution in an organic solvent.

65. The method of claim 60, wherein the solvent in step (d) comprises acetone.

66. The method according to any one of paragraphs 60-65, wherein the temperature of step c) is from 50 to 92 degrees.

67. The method according to claim 60, wherein in step d) of crystallization the mixture is cooled to 5-25°C and stirred for 30-120 minutes.

68. Use of a compound according to any one of claims 1-59 for the treatment and / or prevention of fibrosis.

69. The use according to claim 68, wherein the fibrosis is idiopathic fibrosis.

70. The use according to claim 68 or 69, wherein the fibrosis is selected from pulmonary fibrosis, liver fibrosis, pancreatic fibrosis, cardiac fibrosis (myocardial fibrosis) and renal fibrosis.

71. Use of a compound according to any one of claims 1-59 for the treatment and / or prevention of cough.

72. The use according to claim 71, wherein the cough is a cough accompanying idiopathic pulmonary fibrosis.

73. A method for treating fibrosis in a mammal, comprising administering to said mammal a therapeutically effective amount of a compound according to any one of claims 1-59.

74. The method according to claim 73, wherein the fibrosis is idiopathic fibrosis.

75. A method for treating cough in a mammal, comprising administering to said mammal a therapeutically effective amount of a compound according to any one of claims 1-59.

76. A pharmaceutical composition for the treatment of fibrosis, comprising an effective amount of a compound according to any one of claims 1-59, and a pharmaceutically acceptable carrier.

77. A pharmaceutical composition for treating cough, comprising an effective amount of a compound according to any one of claims 1-59, and a pharmaceutically acceptable carrier.

78. A pharmaceutical composition according to claim 76 or 77, which is a hard gelatin capsule comprising N,N'-bis[2-(1H-imidazol-4-yl)ethyl]oxalamide dihydrochloride dihydrate, lactose, starch and magnesium stearate.

79. The pharmaceutical composition according to item 78, having the following composition, mg / capsule: N,N'-bis[2-(1H-imidazol-4-yl)ethyl]oxalamide dihydrochloride dihydrate from 80 to 120, lactose anhydrous from 75 to 90, pregelatinized starch 1500 from 7 to 15, magnesium stearate from 1 to 5.

80. A pharmaceutical composition according to item 78, having the following composition, mg / capsule: N,N'-bis[2-(1H-imidazol-4-yl)ethyl]oxalamide dihydrochloride dihydrate from 80 to 120, lactose monohydra from 75 to 90, pregelatinized starch 1500 from 7 to 15, magnesium stearate from 1 to 5.

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