Chemical compounds

1. A compound of formula (I)

wherein

m is 2

one R is at the 2 position and is methyl and one R is at the 4 position and is fluoro;

n is 2;

both R 4 are trifluoromethyl and are at the 3 and 5 positions;

R 1 is methyl;

R 2 is methyl;

R 3 is hydrogen; and

R 5 is C(O)CH 3 ;

or a pharmaceutically acceptable salt thereof.

2. 4-(S)-(4-acetyl-piperazin-1-yl)-2-(R)-(4-fluoro-2-methyl-phenyl)-piperidine-1-carboxylic acid, [1-(R)-(3,5-bis-trifluoromethyl-phenyl)-ethyl]-methylamide or a pharmaceutically acceptable salt thereof.

3. 4-(S)-(4-acetyl-piperazin-1-yl)-2-(R)-(4-fluoro-2-methyl-phenyl)-piperidine-1-carboxylic acid, [1-(R)-(3,5-bis-trifluoromethyl-phenyl)-ethyl]-methylamide.

4. The compound according to claim 1 in amorphous form.

5. The compound according to claim 1 in crystalline form.

6. The compound according to claim 2 in amorphous form.

7. The compound according to claim 2 in crystalline form.

8. The compound according to claim 3 in amorphous form.

9. The compound according to claim 3 in crystalline form.

10. A pharmaceutical composition comprising the compound according to claim 1 and one or more pharmaceutically acceptable carriers or excipients.

11. A pharmaceutical composition comprising the compound according to claim 2 and one or more pharmaceutically acceptable carriers or excipients.

12. A pharmaceutical composition comprising the compound according to claim 3 and one or more pharmaceutically acceptable carriers or excipients.

13. The pharmaceutical composition according to claim 10 further comprising a 5HT3 antagonist selected from the group consisting of ondansetron, granisetron and metoclopramide.

14. The pharmaceutical composition according to claim 11 further comprising a 5HT3 antagonist selected from the group consisting of ondansetron, granisetron and metoclopramide.

15. The pharmaceutical composition according to claim 12 further comprising a 5HT3 antagonist selected from the group consisting of ondansetron, granisetron and metoclopramide.

16. A method for the treatment of emesis in a mammal in need thereof comprising administering to said mammal an effective amount of the compound according to claim 1 .

17. A method for the treatment of emesis in a mammal in need thereof comprising administering to said mammal an effective amount of the compound according to claim 2 .

18. A method for the treatment of emesis in a mammal in need thereof comprising administering to said mammal an effective amount of the compound according to claim 3 .

19. The method according to claim 6 , wherein said mammal is man.

20. The method according to claim 17 , wherein said mammal is man.

21. The method according to claim 18 , wherein said mammal is man.

22. The method according to claim 6 , wherein said emesis is delayed emesis.

23. The method according to claim 17 , wherein said emesis is delayed emesis.

24. The method according to claim 18 , wherein said emesis is delayed emesis.

25. The method according to claim 6 , wherein said emesis is anticipatory emesis.

26. The method according to claim 17 , wherein said emesis is anticipatory emesis.

27. The method according to claim 18 , wherein said emesis is anticipatory emesis.

28. The method according to claim 6 , wherein said emesis is induced by cancer chemotherapeutic agents.

29. The method according to claim 17 , wherein said emesis is induced by cancer chemotherapeutic agents.

30. The method according to claim 18 , wherein said emesis is induced by cancer chemotherapeutic agents.

31. The method according to claim 28 , wherein said cancer chemotherapeutic agent is selected from the group consisting of cyclophosphamide, carmustine, lomustine, chlorambucil, dactinomycin, doxorubicin, mitomycin-C, bleomyci n, cytarabine, methotrexate, 5-fluorouracil, etoposide, vinblastine, vincristine, cisplatin, dacarbazine, procarbazine and hydroyurea.

32. The method according to claim 29 , wherein said cancer chemotherapeutic agent is selected from the group consisting of cyclophosphamide, carmustine, lomustine, chlorambucil, dactinomycin, doxorubicin, mitomycin-C, bleomycin, cytarabine, methotrexate, 5-fluorouracil, etoposide, vinblastine, vincristine, cisplatin, dacarbazine, procarbazine and hydroyurea.

33. The method according to claim 30 , wherein said cancer chemotherapeutic agent is selected from the group consisting of cyclophosphamide, carmustine, lomustine, chlorambucil, dactinomycin, doxorubicin, mitomycin-C, bleomyci n, cytarabine, methotrexate, 5-fluorouracil, etoposide, vinblastine, vincristine, cisplatin, dacarbazine, procarbazine and hydroyurea.

34. The method according to claim 16 , wherein said emesis is induced by radiation sickness or radiation therapy.

35. The method according to claim 17 , wherein said emesis is induced by radiation sickness or radiation therapy.

36. The method according to claim 18 , wherein said emesis is induced by radiation sickness or radiation therapy.

37. The method according to claim 16 , wherein said emesis is induced by pregnancy.

38. The method according to claim 17 , wherein said emesis is induced by pregnancy.

39. The method according to claim 18 , wherein said emesis is induced by pregnancy.

40. The method according to claim 16 , wherein said emesis is induced by post-operative sickness.

41. The method according to claim 17 , wherein said emesis is induced by post-operative sickness.

42. The method according to claim 18 , wherein said emesis is induced by post-operative sickness.

43. The method according to claim 16 , wherein said emesis is induced by migraine.

44. The method according to claim 17 , wherein said emesis is induced by migraine.

45. The method according to claim 18 , wherein said emesis is induced by migraine.

46. The method according to claim 16 , wherein said emesis is induced by opiod analgesics.

47. The method according to claim 17 , wherein said emesis is induced by opiod analgesics.

48. The method according to claim 18 , wherein said emesis is induced by opiod analgesics.

49. The method according to claim 16 , further comprising administering an effective amount of a 5HT3 antagonist.

50. The method according to claim 17 , further comprising administering an effective amount of a 5HT3 antagonist.

51. The method according to claim 18 , further comprising administering an effective amount of a 5HT3 antagonist.

52. The method according to claim 49 , wherein said 5HT3 antagonist is selected from the group consisting of ondansetron, granisetron and metoclopramide.

53. The method according to claim 50 , wherein said 5HT3 antagonist is selected from the group consisting of ondansetron, granisetron and metoclopramide.

54. The method according to claim 51 , wherein said 5HT3 antagonist is selected from the group consisting of ondansetron, granisetron and metoclopramide.

55. The method according to claim 16 , further comprising administering an effective amount of ondansetron.

56. The method according to claim 17 , further comprising administering an effective amount of ondansetron.

57. The method according to claim 18 , further comprising administering an effective amount of ondansetron.

58. A method for the treatment of emesis in a mammal being treated with an opiod analgesic, said method comprising administering to said mammal an effective amount of the compound according to claim 1 .

59. The method according to claim 58 , wherein said compound is 4-(S)-(4-acetyl-piperazin-1-yl)-2-(R)-(4-fluoro-2-methyl-phenyl)-piperidine-1-carboxylic acid, [1-(R)-(3,5-bis-trifluoromethyl-phenyl)-ethyl]-methylamide or a pharmaceutically acceptable salt thereof.

60. The method according to claim 58 , wherein said compound is 4-(S)-(4-acetyl-piperazin-1-yl)-2-(R)-(4-fluoro-2-methyl-phenyl)-piperidine-1-carboxylic acid, [1-(R)-(3,5-bis-trifluoromethyl-phenyl)-ethyl]-methylamide.

61. A method for the treatment of emesis in a mammal being treated with an opiod analgesic, said method comprising administering to said mammal an effective amount of 4-(S)-(4-acetyl-piperazin-1-yl)-2-(R)-(4-fluoro-2-methyl-phenyl)-piperidine-1-carboxylic acid, [1-(R)-(3,5-bis-trifl uoromethyl-phenyl)-ethyl]-methylamide methanesulphonate.

62. The method according to claim 58 , wherein said compound is administered prior to, during, or after treatment with said opiod analgesic.

63. The method according to claim 61 , wherein said compound is administered prior to, during, or after treatment with said opiod analgesic.

64. The method according to claim 58 , wherein said mammal is man.

65. The method according to claim 61 , wherein said mammal is man.

66. The method according to claim 58 , wherein said opiod analgesic is morphine.

67. The method according to claim 61 , wherein said opiod analgesic is morphine.