Vinorelbine derivatives

1. A compound of Formula (I) as follows:

where:

R 1 is:

alkyl;

alkenyl;

alkynyl;

aryl;

Cl;

Br;

F;

CN;

SO 2 NHNH 2 ;

SO 2 NR 5 NH 2 ;

SO 2 NR 5 NHR 6 ;

SO 2 NHNHR 5 ;

SO 2 NHNR 5 R 6 ;

CO 2 R 5 ;

SR 5 ;

SSR 5 ;

SOR 5 ;

SO 2 R 5 ;

SO 2 NHR 5 ;

SO 2 NR 5 R 6 ;

B(OR 5 ) 2 ;

CF 3 ;

SH;

SO 2 NH 2 ;

NH 2 ;

NHR 5 ;

NHCOR 5 ;

NHSO 2 R 5 ;

NR 5 R 6 ;

NR 5 COR 6 ; or

NR 5 SO 2 R 6 ;

R 5 and R 6 can form a ring;

R 2 =alkyl or CH(O);

R 3 =hydrogen, alkyl, or C(O)R 5 ;

R 4 =hydrogen or C(O)R 5 ;

R 5 and R 6 each are independently alkyl, alkenyl, alkynyl, or aryl;

X=OR 5 , NR 5 R 6 , NHNH 2 , NHNHC(O)R 5 , OH, NHR 5 , NH 2 , or NHNHC(O)H;

R 4 and X may be linked together with intervening atoms to form a ring; or a pharmaceutically acceptable salt thereof, wherein the alkyl and alkenyl groups may be branched or straight.

2. The compound according to claim 1 , wherein R 3 =acetyl.

3. The compound according to claim 1 , wherein R 4 =hydrogen.

4. The compound according to claim 1 , wherein X=OMe.

5. The compound according to claim 1 , wherein R 3 =acetyl, R 4 =hydrogen, and X=OMe.

6. The compound according to claim 1 , wherein R 2 =CH(O).

7. The compound according to claim 1 , wherein R 2 =alkyl.

8. The compound according to claim 1 , wherein the compound has the following chemical formula:

9. The compound according to claim 1 , wherein the compound has the following chemical formula:

10. The compound according to claim 1 , wherein the compound has a substituted form of R 1 with the following chemical formula:

11. The compound according to claim 1 , wherein the compound has a substituted form of R 1 with the following chemical formula:

12. The compound according to claim 1 , wherein the compound has a substituted form of R 1 with the following chemical formula:

13. The compound according to claim 1 , wherein the compound has a substituted form of R 1 with the following chemical formula:

14. The compound according to claim 1 , wherein the compound has the following chemical formula:

15. The compound according to claim 1 , wherein the compound has a substituted form of R 1 with the following chemical formula:

16. The compound according to claim 1 , wherein the compound has the following chemical formula:

17. The compound according to claim 1 , wherein the compound has the following chemical formula:

18. The compound according to claim 1 , wherein the compound has a substituted form of R 1 with the following chemical formula:

19. The compound according to claim 1 , wherein the compound has a substituted form of R 1 with the following chemical formula:

20. The compound according to claim 1 , wherein the compound has a substituted form of R 1 with the following chemical formula:

21. The compound according to claim 1 , wherein the compound has a substituted form of R 1 with the following chemical formula:

22. The compound according to claim 1 , wherein the compound has a substituted form of R 1 with the following chemical formula:

23. The compound according to claim 1 , wherein the compound has the following chemical formula:

24. The compound according to claim 1 , wherein the compound has a substituted form of R 1 with the following chemical formula:

25. The compound according to claim 1 , wherein the compound has a substituted form of R 1 with the following chemical formula:

26. The compound according to claim 1 , wherein the compound has a substituted form of R 1 with the following chemical formula:

27. The compound according to claim 1 , wherein the compound has the following chemical formula:

28. The compound according to claim 1 , wherein the compound has the following chemical formula:

29. The compound according to claim 1 , wherein the compound has the following chemical formula:

30. The compound according to claim 1 , wherein the compound has a substituted form of R 1 with the following chemical formula:

31. The compound according to claim 1 , wherein the compound has the following chemical formula:

32. The compound according to claim 1 , wherein the compound has the following chemical formula:

33. The compound according to claim 1 , wherein the compound has a substituted form of R 1 with the following chemical formula:

34. The compound according to claim 1 , wherein the compound has a substituted form of R 1 with the following chemical formula:

35. The compound according to claim 1 , wherein the compound has the following chemical formula:

36. The compound according to claim 1 , wherein the compound has a substituted form of R 1 with the following chemical formula:

37. The compound with the following chemical formula:

38. The compound according to claim 1 , wherein the compound has the following chemical formula:

39. The compound according to claim 1 , wherein the compound has the following chemical formula:

40. A complex comprising 2 structures of Formula I, according to claim 1 , joined together at their R 1 groups, wherein each R 1 is —S—.

41. A process for preparation of a derivative product compound of Formula (I) as follows:

where:

R 1 is:

alkyl;

alkenyl;

alkynyl;

aryl;

CN;

CH(O);

COR 5 ;

SO 2 NHNH 2 ;

SO 2 NR 5 NH 2 ;

SO 2 NR 5 NHR 6 ;

SO 2 NHNHR 5 ;

SO 2 NHNR 5 R 6 ;

CO 2 R 5 ;

SR 5 ;

SSR 5 ;

SOR 5 ;

SO 2 R 5 ;

SO 2 NHR 5 ;

SO 2 NR 5 R 6 ;

B(OR 5 ) 2 ;

CF 3 ;

SH;

SO 2 NH 2 ;

NH 2 ;

NHR 5 ;

NHCOR 5 ;

NHSO 2 R 5 ;

NR 5 R 6 ;

NR 5 COR 6 ; or

NR 5 SO 2 R 6 ;

R 5 and R 6 can form a ring;

R 2 =alkyl or CH(O);

R 3 =hydrogen, alkyl, or C(O)R 5 ;

R 4 =hydrogen or C(O)R 5 ;

R 5 and R 6 each are independently alkyl, alkenyl, alkynyl, and aryl;

X=OR 5 , NR 5 R 6 , NHNH 2 , NHNHC(O)R 5 , OH, NHR 5 , NH 2 , or NHNHC(O)H;

R 4 and X may be linked together with intervening atoms to form a ring; or a pharmaceutically acceptable salt thereof, wherein the alkyl and alkenyl groups may be branched or straight, said process comprising:

converting an intermediate compound of formula:

wherein Y is a halogen,

under conditions effective to produce the product compound of Formula (I).

42. The process of claim 41 further comprising:

halogenating a starting material compound of formula:

under conditions effective to form the intermediate compound.

43. The process of claim 42 , wherein said halogenating is carried out with a halogenating agent selected from the group consisting of N-bromosuccinimide, N-iodosuccinimide, and iodine monochloride.

44. The process of claim 42 , wherein the conditions effective to form the intermediate compound include enzymatic bromination.

45. The process of claim 41 , wherein said converting comprises:

reacting the intermediate compound with a palladium catalyst reagent to produce the product of Formula (I).

46. The process of claim 45 , wherein the palladium catalyst reagent is selected from the group consisting of palladium acetate, tris(dibenzylideneacetone)dipalladium(0), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), tetrakis(triphenylphosphine)palladium, and bis(triphenylphosphine)palladium(II)dichloride.

47. A process for preparation of a derivative product compound of Formula (I) as follows:

where:

R 1 is halogen;

R 2 =alkyl or CH(O);

R 3 =hydrogen, alkyl, or C(O)R 5 ;

R 4 =hydrogen or C(O)R 5 ;

R 5 and R 6 each are independently alkyl, alkenyl, alkynyl, or aryl;

X=OR 5 , NR 5 R 6 , NHNH 2 , NHNHC(O)R 5 , OH, NHR 5 , NH 2 , or NHNHC(O)H;

R 4 and X may be linked together with intervening atoms to form a ring; or a pharmaceutically acceptable salt thereof, wherein the alkyl and alkenyl groups may be branched or straight, said process comprising:

halogenating a starting material compound of formula:

under conditions effective to form the derivative product compound.

48. The process of claim 47 , wherein said halogenating is carried out with a halogenating agent selected from the group consisting of N-bromosuccinimide, N-iodosuccinimide, and iodine monochloride.

49. The process of claim 47 , wherein the conditions effective to form the intermediate compound include enzymatic bromination.

50. A composition of matter comprising the compound of claim 1 and one or more pharmaceutical excipients.

51. The composition according to claim 50 , wherein R 3 =acetyl.

52. The composition according to claim 50 , wherein R 4 =hydrogen.

53. The composition according to claim 50 , wherein X=OMe.

54. The composition according to claim 50 , wherein R 3 =acetyl, R 4 =hydrogen, and X=OMe.

55. The composition according to claim 50 , wherein R 2 =CH(O).

56. The composition according to claim 50 , wherein R 2 =alkyl.