Pyridoindolobenz[b,d]azepine derivatives and uses thereof

1. A compound of Formula I,

Y is a single bond or a double bond;

A and B are independently —(CH 2 ) n —;

subscript ‘n’ varies from 0 to 3;

R 1 is selected from the group consisting of hydrogen, C 1 -C 10 alkyl, C 1 -C 10 hydroxyalkyl, C 5 -C 10 aryl, C 1 -C 15 aroylalkyl, C 1 -C 10 alkoxycarbonylalkyl, C 5 -C 10 arylalkyl, and C 1 -C 10 carbamoylalkyl;

R 2 is selected from the group consisting of hydrogen, C 1 -C 10 alkyl, C 5 -C 10 aryl, and C 5 -C 10 arylalkyl;

each of R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , and R 10 is independently selected from the group consisting of hydrogen, C 1 -C 10 alkyl, hydroxyl, C 1 -C 10 alkoxyl, —NR 11 R 12 , C 1 -C 10 hydroxyalkyl, halogen, trihaloalkyl, cyano, carboxyl, C 1 -C 10 acyl, C 1 -C 10 alkoxyalkyl; C 1 -C 10 alkoxycarbonyl, C 5 -C 10 aryl, and C 5 -C 10 arylalkyl; and

R 11 and R 12 are independently hydrogen or C 1 -C 10 alkyl.

2. The compound of claim 1 , wherein Y is a double bond;

A is —CH 2 —; and

B is —CH 2 CH 2 —.

3. The compound of claim 2 , wherein

R 1 is selected from the group consisting of hydrogen, C 1 -C 10 alkyl, C 1 -C 10 hydroxyalkyl, C 5 -C 10 arylalkyl, and C 1 -C 10 carbamoylalkyl;

R 2 and R 3 are hydrogens; and

each of R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , and R 10 is independently selected from the group consisting of hydrogen, C 1 -C 10 alkyl, hydroxyl, C 1 -C 10 alkoxyl, and halogen.

4. The compound of claim 3 , wherein

each of R 4 , R 5 , R 6 , and R 7 is independently selected from the group consisting of hydrogen, C 1 -C 10 alkyl, hydroxyl, C 1 -C 10 alkoxyl, and halogen; and

R 8 , R 9 , and R 10 are hydrogens.

5. The compound of claim 3 , wherein

R 4 , R 5 , R 6 , and R 7 are hydrogens; and

each of R 8 , R 9 , and R 10 is independently selected from the group consisting of hydrogen, C 1 -C 10 alkyl, hydroxyl, C 1 -C 10 alkoxyl, and halogen.

6. The compound of claim 4 , wherein

R 1 is hydrogen, C 1 -C 10 alkyl, CH 2 Ph, CH 2 CH 2 OH, or CH 2 CONH 2 ; and

each of R 4 , R 5 , R 6 , and R 7 is hydrogen, CH 3 , hydroxyl, OCH 3 , F, or Cl.

7. The compound of claim 5 , wherein

R 1 is hydrogen, C 1 -C 10 alkyl, CH 2 Ph, CH 2 CH 2 OH, or CH 2 CONH 2 ; and

each of R 8 , R 9 , and R 10 is hydrogen, CH 3 , hydroxyl, OCH 3 , F, or Cl.

8. The compound of claim 7 , wherein R 1 is hydrogen or CH 3 ; and

R 8 , R 9 , and R 10 are hydrogens.

9. The compound of claim 1 , wherein A is —CH 2 —; B is —CH 2 CH 2 —;

and Y is a single bond with cis-fused B|C rings represented by the stereoisomeric structural Formulas IIa or IIb,

10. The compound of claim 9 , wherein

R 1 is selected from the group consisting of hydrogen, C 1 -C 10 alkyl, C 1 -C 10 hydroxyalkyl, C 5 -C 10 arylalkyl, and C 1 -C 10 carbamoylalkyl;

R 2 and R 3 are hydrogens; and

each of R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , and R 10 is independently selected from the group consisting of hydrogen, C 1 -C 10 alkyl, hydroxyl, C 1 -C 10 alkoxyl, and halogen.

11. The compound of claim 10 , wherein

each of R 4 , R 5 , R 6 , and R 7 is independently selected from the group consisting of hydrogen, C 1 -C 10 alkyl, hydroxyl, C 1 -C 10 alkoxyl, and halogen; and

R 8 , R 9 , and R 10 are hydrogens.

12. The compound of claim 10 , wherein

R 4 , R 5 , R 6 , and R 7 are hydrogens; and

each of R 8 , R 9 , and R 10 is independently selected from the group consisting of hydrogen, C 1 -C 10 alkyl, hydroxyl, C 1 -C 10 alkoxyl, and halogen.

13. The compound of claim 11 , wherein

R 1 is hydrogen, C 1 -C 10 alkyl, CH 2 Ph, CH 2 CH 2 OH, or CH 2 CONH 2 ; and

each of R 4 , R 5 , R 6 , and R 7 is hydrogen, CH 3 , hydroxyl, OCH 3 , F, or Cl.

14. The compound of claim 12 , wherein

R 1 is hydrogen, C 1 -C 10 alkyl, CH 2 Ph, CH 2 CH 2 OH, or CH 2 CONH 2 ; and

each of R 8 , R 9 , and R 10 is hydrogen, CH 3 , hydroxyl, OCH 3 , F, or Cl.

15. The compound of claim 14 , wherein R 1 is hydrogen or CH 3 ; and

R 8 , R 9 , and R 10 are hydrogens.

16. The compound of claim 1 , wherein A is —CH 2 —; B is —CH 2 CH 2 —;

and Y is a single bond with trans-fused B|C rings represented by the stereoisomeric structural Formulas IIIa or IIIb,

17. The compound of claim 16 , wherein

R 1 is selected from the group consisting of hydrogen, C 1 -C 10 alkyl, C 1 -C 10 hydroxyalkyl, C 5 -C 10 arylalkyl, and C 1 -C 10 carbamoylalkyl;

R 2 and R 3 are hydrogens; and

each of R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , and R 10 is independently selected from the group consisting of hydrogen, C 1 -C 10 alkyl, hydroxyl, C 1 -C 10 alkoxyl, and halogen.

18. The compound of claim 17 , wherein

each of R 4 , R 5 , R 6 , and R 7 is independently selected from the group consisting of hydrogen, C 1 -C 10 alkyl, hydroxyl, C 1 -C 10 alkoxyl, and halogen; and

R 8 , R 9 , and R 10 are hydrogens.

19. The compound of claim 17 , wherein

R 4 , R 5 , R 6 , and R 7 are hydrogens; and

each of R 8 , R 9 , and R 10 is independently selected from the group consisting of hydrogen, C 1 -C 10 alkyl, hydroxyl, C 1 -C 10 alkoxyl, and halogen.

20. The compound of claim 18 , wherein

R 1 is hydrogen, C 1 -C 10 alkyl, CH 2 Ph, CH 2 CH 2 OH, or CH 2 CONH 2 ; and

each of R 4 , R 5 , R 6 , and R 7 is hydrogen, CH 3 , hydroxyl, OCH 3 , F, or Cl.

21. The compound of claim 19 , wherein

R 1 is hydrogen, C 1 -C 10 alkyl, CH 2 Ph, CH 2 CH 2 OH, or CH 2 CONH 2 ; and

each of R 8 , R 9 , and R 10 is hydrogen, CH 3 , hydroxyl, OCH 3 , F, or Cl.

22. The compound of claim 21 , wherein R 1 is hydrogen or CH 3 ; and

R 8 , R 9 , and R 10 are hydrogens.

23. A pharmaceutical preparation comprising the compound of claim 8 in a pharmaceutically acceptable formulation for administration to a patient.

24. The pharmaceutical preparation of claim 8 , in which the formulation is pharmaceutically acceptable for oral administration.

25. The pharmaceutical preparation of claim 8 , in which the formulation is pharmaceutically acceptable for topical administration.

26. A method of alleviating pain comprising administering an effective amount of pharmaceutically acceptable composition of Formula I, wherein

Y is a single bond or a double bond;

A and B are independently —(CH 2 ) n —;

subscript ‘n’ varies from 0 to 3;

R 1 is selected from the group consisting of hydrogen, C 1 -C 10 alkyl, C 1 -C 10 hydroxyalkyl, C 5 -C 10 aryl, C 1 -C 15 aroylalkyl, C 1 -C 10 alkoxycarbonylalkyl, C 5 -C 10 arylalkyl, and C 1 -C 10 carbamoylalkyl;

R 2 is selected from the group consisting of hydrogen, C 1 -C 10 alkyl, C 5 -C 10 aryl, and C 5 -C 10 arylalkyl;

each of R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , and R 10 is independently selected from the group consisting of hydrogen, C 1 -C 10 alkyl, hydroxyl, C 1 -C 10 alkoxyl, —NR 11 R 12 , C 1 -C 10 hydroxyalkyl, halogen, trihaloalkyl, cyano, carboxyl, C 1 -C 10 acyl, C 1 -C 10 alkoxyalkyl; C 1 -C 10 alkoxycarbonyl, C 5 -C 10 aryl, and C 5 -C 10 arylalkyl; and

R 11 and R 12 are independently hydrogen or C 1 -C 10 alkyl.

27. The method of claim 26 , wherein Y is a double bond;

A is —CH 2 —; and

B is —CH 2 CH 2 —.

28. The method of claim 27 , wherein

R 1 is selected from the group consisting of hydrogen, C 1 -C 10 alkyl, C 1 -C 10 hydroxyalkyl, C 5 -C 10 arylalkyl, and C 1 -C 10 carbamoylalkyl;

R 2 and R 3 are hydrogens; and

each of R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , and R 10 is independently selected from the group consisting of hydrogen, C 1 -C 10 alkyl, hydroxyl, C 1 -C 10 alkoxyl, and halogen.

29. The method of claim 28 , wherein

each of R 4 , R 5 , R 6 , and R 7 is independently selected from the group consisting of hydrogen, C 1 -C 10 alkyl, hydroxyl, C 1 -C 10 alkoxyl, and halogen; and

R 8 , R 9 , and R 10 are hydrogens.

30. The method of claim 28 , wherein

R 4 , R 5 , R 6 , and R 7 are hydrogens; and

each of R 8 , R 9 , and R 10 is independently selected from the group consisting of hydrogen, C 1 -C 10 alkyl, hydroxyl, C 1 -C 10 alkoxyl, and halogen.

31. The method of claim 29 , wherein

R 1 is hydrogen, C 1 -C 10 alkyl, CH 2 Ph, CH 2 CH 2 OH, or CH 2 CONH 2 ; and

each of R 4 , R 5 , R 6 , and R 7 is hydrogen, CH 3 , hydroxyl, OCH 3 , F, or Cl.

32. The method of claim 30 , wherein

R 1 is hydrogen, C 1 -C 10 alkyl, CH 2 Ph, CH 2 CH 2 OH, or CH 2 CONH 2 ; and

each of R 8 , R 9 , and R 10 is hydrogen, CH 3 , hydroxyl, OCH 3 , F, or Cl.

33. The method of claim 32 , wherein R 1 is hydrogen or CH 3 ; and

R 8 , R 9 , and R 10 are hydrogens.

34. The method of claim 26 , wherein A is —CH 2 —; B is —CH 2 CH 2 —;

and Y is a single bond with cis-fused B|C rings represented by the stereoisomeric structural Formulas IIa or IIIb,

35. The method of claim 34 , wherein

R 1 is selected from the group consisting of hydrogen, C 1 -C 10 alkyl, C 1 -C 10 hydroxyalkyl, C 5 -C 10 arylalkyl, and C 1 -C 10 carbamoylalkyl;

R 2 and R 3 are hydrogens; and

each of R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , and R 10 is independently selected from the group consisting of hydrogen, C 1 -C 10 alkyl, hydroxyl, C 1 -C 10 alkoxyl, and halogen.

36. The method of claim 35 , wherein

each of R 4 , R 5 , R 6 , and R 7 is independently selected from the group consisting of hydrogen, C 1 -C 10 alkyl, hydroxyl, C 1 -C 10 alkoxyl, and halogen; and

R 8 , R 9 , and R 10 are hydrogens.

37. The method of claim 35 , wherein

R 4 , R 5 , R 6 , and R 7 are hydrogens; and

each of R 8 , R 9 , and R 10 is independently selected from the group consisting of hydrogen, C 1 -C 10 alkyl, hydroxyl, C 1 -C 10 alkoxyl, and halogen.

38. The method of claim 36 , wherein

R 1 is hydrogen, C 1 -C 10 alkyl, CH 2 Ph, CH 2 CH 2 OH, or CH 2 CONH 2 ; and

each of R 4 , R 5 , R 6 , and R 7 is hydrogen, CH 3 , hydroxyl, OCH 3 , F, or Cl.

39. The method of claim 37 , wherein

R 1 is hydrogen, C 1 -C 10 alkyl, CH 2 Ph, CH 2 CH 2 OH, or CH 2 CONH 2 ; and

each of R 8 , R 9 , and R 10 is hydrogen, CH 3 , hydroxyl, OCH 3 , F, or Cl.

40. The method of claim 39 , wherein R 1 is hydrogen or CH 3 ; and

R 8 , R 9 , and R 10 are hydrogens.

41. The method of claim 26 , wherein A is —CH 2 —; B is —CH 2 CH 2 —;

and Y is a single bond with trans-fused B|C rings represented by the stereoisomeric structural Formulas IIIa or IIIb,

42. The method of claim 41 , wherein

R 1 is selected from the group consisting of hydrogen, C 1 -C 10 alkyl, C 1 -C 10 hydroxyalkyl, C 5 -C 10 arylalkyl, and C 1 -C 10 carbamoylalkyl;

R 2 and R 3 are hydrogens; and

each of R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , and R 10 is independently selected from the group consisting of hydrogen, C 1 -C 10 alkyl, hydroxyl, C 1 -C 10 alkoxyl, and halogen.

43. The method of claim 42 , wherein

each of R 4 , R 5 , R 6 , and R 7 is independently selected from the group consisting of hydrogen, C 1 -C 10 alkyl, hydroxyl, C 1 -C 10 alkoxyl, and halogen; and

R 8 , R 9 , and R 10 are hydrogens.

44. The method of claim 42 , wherein

R 4 , R 5 , R 6 , and R 7 are hydrogens; and

each of R 8 , R 9 , and R 10 is independently selected from the group consisting of hydrogen, C 1 -C 10 alkyl, hydroxyl, C 1 -C 10 alkoxyl, and halogen.

45. The method of claim 43 , wherein

R 1 is hydrogen, C 1 -C 10 alkyl, CH 2 Ph, CH 2 CH 2 OH, or CH 2 CONH 2 ; and

each of R 4 , R 5 , R 6 , and R 7 is hydrogen, CH 3 , hydroxyl, OCH 3 , F, or Cl.

46. The method of claim 44 , wherein

R 1 is hydrogen, C 1 -C 10 alkyl, CH 2 Ph, CH 2 CH 2 OH, or CH 2 CONH 2 ; and

each of R 8 , R 9 , and R 10 is hydrogen, CH 3 , hydroxyl, OCH 3 , F, or Cl.

47. The method of claim 46 , wherein R 1 is hydrogen or CH 3 ; and

R 8 , R 9 , and R 10 are hydrogens.

48. The method of claim 26 , wherein said pain arises from neuropathy.

49. The method of claim 26 , wherein said pain arises from inflammation.

50. The method of claim 26 , wherein said pain arises from arthritis.

51. The method of claim 26 , wherein said pain arises from cancer.