3-aryl-3-hydroxy-2-amino-propionic acid amides, 3-heteroaryl-3-hydroxy-2-amino-propionic acid amides and related compounds having analgesic and/or immuno stimulant activity

1. A compound of the formula

or a pharmaceutically acceptable salt thereof, where:

R 1 is H or alkyl of 1 to 6 carbons;

R 2 is selected from the group consisting of H, and alkyl of 1 to 6 carbons; or the R 1 and R 2 groups together with the nitrogen atom to which they are shown attached form a saturated or unsaturated 4, 5, 6 or 7 membered ring that optionally includes one or two heteroatoms independently selected from the group consisting of N, O and S, said 4, 5, 6 or 7 membered ring optionally being substituted with one or two COOH, CH 2 OH, OH, B(OH) 2 , halogen groups, cyano groups, or with one or two alkyl groups having 1 to 6 carbons, or one or two carbons of said rings being attached to an oxygen to form keto groups and said 4, 5, 6 or 7 membered ring optionally being condensed with an aromatic or non-aromatic 5 or 6 membered ring that optionally includes heteroatoms selected from N, O and S;

R 3 is independently selected from the group consisting of H, alkyl of 1 to 20 carbons, cycloalkyl of 3 to 6 carbons, aryl or heteroaryl, aryl-alkyl where the alkyl moiety has 1 to 4 carbons, aryl-(hydroxy)alkyl where the alkyl moiety has 1 to 4 carbons, and heteroaryl-alkyl where the alkyl moiety has 1 to 4 carbons, and hetero-(hydroxy)alkyl where the alkyl moiety has 1 to 4 carbons, said aryl or heteroaryl groups being optionally substituted with 1 to 3 groups independently selected from the group consisting of halogen, alkyl of 1 to 6 carbons, alkoxy of 1 to 6 carbons and thioxy of 1 to 3 carbons, or R 3 is CO—R 7 , SO 2 R 7 or CO—O—R 7 where R 7 is H, alkyl of 1 to 1 to 20 carbons, alkyl of 1 to 20 carbons substituted with and NH 2 group or with an NH—COalkyl group where the alkyl group has one to 6 carbons, aryl or heteroaryl, aryl-alkyl where the alkyl moiety has 1 to 4 carbons or heteroaryl-alkyl where the alkyl moiety has 1 to 4 carbons, said aryl or heteroaryl groups being optionally substituted with 1 to 3 groups independently selected from the group consisting of halogen, alkyl of 1 to 6 carbons, alkoxy of 1 to 6 carbons and thioxy of 1 to 3 carbons;

R 4 is H, alkyl of 1 to 6 carbons or CO—R 8 where R 8 is alkyl of 1 to 6 carbons;

the wavy lines represent bonds connected to carbons having R or S configuration;

the dashed lines represent a bond or absence of a bond with the proviso that the ring containing the dashed lines is aromatic;

m, n and q are independently 1;

s is zero (0);

X represents N;

W, and Y independently represent CH;

R 5 and R 6 are independently selected from the group consisting of H, phenyl, halogen, alkyl of 1 to 6 carbons, halogen substituted alkyl of 1 to 6 carbons, alkoxy of 1 to 6 carbons and thioxy of 1 to 3 carbons; or

R 5 and R 6 together with the atoms to which they are attached jointly form a carbocyclic or a heterocyclic ring, the carbocyclic ring having 5 or 6 atoms in the ring, the heterocyclic ring having 5 or 6 atoms in the ring and 1 to 3 heteroatoms independently selected from N, O and S;

said carbocyclic or heterocyclic ring jointly formed by R 5 and R 6 being optionally substituted with 1 to 6 R 9 groups where R 9 is independently selected from the group consisting of halogen, alkyl of 1 to 6 carbons, alkoxy of 1 to 6 carbons and thioxy of 1 to 3 carbons.

2. A compound in accordance with claim 1 where R 4 is H.

3. A compound in accordance with claim 2 where both R 3 groups are H.

4. A compound in accordance with claim 2 where one R 3 group is H and the other R 3 group is CO—R 7 or alkyl of 1 to 20 carbons.

5. A compound in accordance with claim 2 where R 3 is independently selected from the group consisting of H and alkyl of 1 to 10 carbons.

6. A compound in accordance with claim 1 where R 4 is CO—R 8 .

7. A compound in accordance with claim 1 where R 1 and R 2 together with the nitrogen form a 4, 5, 6 or 7 membered ring.

8. A compound in accordance with claim 7 where R 1 and R 2 together with the nitrogen form a 5 membered ring.

9. A compound in accordance with claim 7 where R 1 and R 2 together with the nitrogen form a 6 membered ring.

10. A compound in accordance with claim 1 where both R 5 and R 6 are hydrogen.

11. A compound of the formula

or a pharmaceutically acceptable salt thereof, where:

R 1 is H or alkyl of 1 to 6 carbons;

R 2 is selected from the group consisting of H, and alkyl of 1 to 6 carbons; or the R 1 and R 2 groups together with the nitrogen atom to which they are shown attached form a saturated or unsaturated 4, 5, 6 or 7 membered ring that optionally additionally includes one or two heteroatoms independently selected from the group consisting of N, O and S, said 4, 5, 6 or 7 membered ring optionally being substituted with one or two COOH, CH 2 OH, OH, B(OH) 2 , halogen groups, cyano groups or with one or two alkyl groups having 1 to 6 carbons;

R 3 is H, CO—R 7 or CO—O—R 7 where R 7 is H, alkyl of 1 to 1 to 20 carbons, cycloalkyl of 3 to 6 carbons, aryl or heteroaryl, aryl-alkyl, aryl(hydroxy)alkyl, heteroaryl-alkyl or heteroalkyl(hydroxy)alkyl where the alkyl moiety has 1 to 4 carbons, said aryl or heteroaryl groups being optionally substituted with 1 to 3 groups independently selected from the group consisting of halogen, alkyl of 1 to 6 carbons, alkoxy of 1 to 6 carbons and thioxy of 1 to 3 carbons;

R 4 is H, alkyl of 1 to 6 carbons, or CO—R 8 where R 8 is alkyl of 1 to 6 carbons;

R 5 and R 6 are independently selected from the group consisting of H, halogen, alkyl of 1 to 6 carbons, alkoxy of 1 to 6 carbons and thioxy of 1 to 3 carbons; or

R 5 and R 6 together with the atoms to which they are attached jointly form a carbocyclic or a heterocyclic ring, the carbocyclic ring having 5 or 6 atoms in the ring, the heterocyclic ring having 5 or 6 atoms in the ring and 1 to 3 heteroatoms independently selected from N, O and S;

said carbocyclic or heterocyclic ring jointly formed by R 5 and R 6 being optionally substituted with 1 to 6 R 9 groups where R 9 is independently selected from halogen, alkyl of 1 to 6 carbons, alkoxy of 1 to 6 carbons, and

the wavy lines represent bonds of the alpha or beta configuration.

12. A compound in accordance with claim 11 where R 4 is H.

13. A compound in accordance with claim 11 where both R 3 groups are H.

14. A compound in accordance with claim 11 where both R 5 and R 6 are hydrogen.

15. A compound of the formula

or a pharmaceutically acceptable salt of said compound, wherein:

R 1 and R 2 groups together with the nitrogen atom to which the are shown attached form a saturated 5 or 6 membered ring, said ring optionally being substituted with one or two COOH CH 2 OH, OH, B(OH) 2 , halogen groups, cyano groups or with one or two alkyl groups haying 1 to 6 carbons;

R 3 is H or alkyl of 1 to 20 carbons; and

R 4 is H or alkyl of 1 to 6 carbons.

16. A compound in accordance with claim 15 where R 4 is H.

17. A compound in accordance with claim 15 where both R 3 groups are H.

18. A compound of the formula

or a pharmaceutically acceptable salt of said compound.

19. A compound of formula

or a pharmaceutically acceptable salt of said compound.

20. A compound in accordance with claim 15 having the formula

or any other pharmaceutically acceptable salt of

21. A compound in accordance with claim 15 having the formula

or any other pharmaceutically acceptable salt of

22. A compound in accordance with claim 15 having the formula

or any other pharmaceutically acceptable salt of

23. A compound in accordance with claim 15 having the formula

or any other pharmaceutically acceptable salt of

24. A compound in accordance with claim 15 having the formula

or any other pharmaceutically acceptable salt of

25. A compound in accordance with claim 15 having the formula

or any other pharmaceutically acceptable salt

26. A compound of the formula

or any other pharmaceutically acceptable salt of

27. A compound of the formula

or any other pharmaceutically acceptable salt of

28. A compound of the formula

or any other pharmaceutically acceptable salt of

29. A compound of the formula

or a pharmaceutically acceptable salt of said compound.

30. A compound in accordance with claim 11 having the formula

or any other pharmaceutically acceptable salt of

31. A compound in accordance with claim 11 having the formula

or any other pharmaceutically acceptable salt of

32. A compound in accordance with claim 11 having the formula

or any other pharmaceutically acceptable salt of

33. A compound in accordance with claim 11 having the formula

or any other pharmaceutically acceptable salt of

34. A compound in accordance with claim 11 having the formula

or any other pharmaceutically acceptable salt of

35. A compound in accordance with claim 11 having the formula

or any other pharmaceutically acceptable salt of

36. A compound in accordance with claim 11 having the formula

or any other pharmaceutically acceptable salt of

37. A compound in accordance with claim 11 having the formula

or any other pharmaceutically acceptable salt of

38. A compound in accordance with claim 37 having the formula

or any other pharmaceutically acceptable salt of

39. A compound in accordance with claim 37 having the formula

or any other pharmaceutically acceptable salt of

40. A method of treating pain in a mammal in need of such treatment, comprising administering to said mammal at least one compound in accordance with claim 1 or a pharmaceutically acceptable salt thereof.

41. A compound of the formula

or a pharmaceutically acceptable salt thereof.

42. A pharmaceutical composition comprising at least one compound of claim 1 or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient.

43. A pharmaceutical composition comprising at least one compound of claim 11 or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient.

44. A pharmaceutical composition comprising at least one compound of claim 15 or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient.

45. A pharmaceutical composition comprising the compound of claim 18 or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient.

46. A pharmaceutical composition comprising the compound of claim 19 or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient.

47. A pharmaceutical composition comprising at least one compound of claim 26 , and at least one pharmaceutically acceptable excipient.

48. A pharmaceutical composition comprising at least one compound of claim 27 , and at least one pharmaceutically acceptable excipient.

49. A pharmaceutical composition comprising at least one compound of claim 28 , and at least one pharmaceutically acceptable excipient.

50. A pharmaceutical composition comprising at least one compound of claim 29 , and at least one pharmaceutically acceptable excipient.

51. A pharmaceutical composition comprising the compound of claim 41 or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient.

52. A method of treating pain in a mammal in need of such treatment, comprising administering to said mammal at least one compound in accordance with claim 11 or a pharmaceutically acceptable salt thereof.

53. A method of treating pain in a mammal in need of such treatment, comprising administering to said mammal at least one compound in accordance with claim 15 or a pharmaceutically acceptable salt thereof.

54. A method of treating pain in a mammal in need of such treatment, comprising administering to said mammal at least one compound in accordance with claim 28 .

55. A method of treating pain in a mammal in need of such treatment, comprising administering to said mammal the compound in accordance with claim 41 or a pharmaceutically acceptable salt thereof.

56. The method of claim 40 , wherein said pain is chronic pain.

57. The method of claim 52 , wherein said pain is chronic pain.

58. The method of claim 53 , wherein said pain is chronic pain.

59. The method of claim 54 , wherein said pain is chronic pain.

60. The method of claim 55 , wherein said pain is chronic pain.