IP Library › Granted Patent US 8,053,428
Granted Patent B2
US 8,053,428 · App. 11/697,370 · Granted Nov 8, 2011

Vinorelbine derivatives

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Quick Facts
Patent No.
US 8,053,428
App. No.
11/697,370
Granted
Nov 8, 2011
Kind
B2
Abstract

The present invention relates to novel vinorelbine derivatives. Pharmaceutical compositions containing these compounds as well as processes of preparation and processes of use for treatment of various conditions are also disclosed.

Claims (136)

1. A method for treating a condition selected from the group consisting of Hodgkin's Disease, breast cancer, and non-small cell lung cancer in mammals, said method comprising:

administering to the mammal a therapeutically effective amount of a compound of Formula (I) as follows:

where:

R 1 is:

alkenyl;

alkynyl;

aryl;

heterocyclyl;

halogen;

CN;

CH(O);

COR 5 ;

SO 2 NHNH 2 ;

SO 2 NR 5 NH 2 ;

SO 2 NR 5 NHR 6 ;

SO 2 NR 5 NR 6 R 7 ;

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, aryl, or heterocyclyl;

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, straight, unsubstituted, and/or substituted and wherein the aryl, alkynyl, and heterocyclyl groups are substituted or unsubstituted.

2. The method according to claim 1 , wherein R 3 =hydrogen.

3. The method according to claim 1 , wherein R 4 =acetyl.

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

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

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

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

8. The method of claim 1 , wherein the mammal is human.

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

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

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

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

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

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

15. The method 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 a substituted form of R 1 with the following chemical formula:

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

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

19. The compound method to claim 1 , wherein the compound has the following chemical formula:

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

21. The method according to claim 1 , wherein

R 1 =alkenyl, alkynyl, CN, SR 5 , or CF 3

R 2 =alkyl or CH(O)

R 5 =alkyl, alkenyl, alkynyl, aryl, or heterocyclyl.

22. The method according to claim 1 , wherein

R 1 =alkenyl, alkynyl, CN or SR 5

R 2 =alkyl

R 5 =alkyl, alkenyl, alkynyl, aryl, or heterocyclyl.

23. The method according to claim 1 , wherein

R 1 =SR 5 ,

R 2 =methyl

R 5 =alkyl.

24. A method for treating a condition selected from the group consisting of advanced ovarian cancer, non-Hodgkin's lymphoma, Karposi's syndrome, leukemic lymphoma, and chronic myeloid leukemia in mammals, said method comprising:

administering to the mammal a therapeutically effective amount of a compound of Formula (I) as follows:

where:

R 1 is:

alkenyl;

alkynyl;

aryl;

heterocyclyl;

halogen;

CN;

CH(O);

COR 5 ;

SO 2 NHNH 2 ;

SO 2 NR 5 NH 2 ;

SO 2 NR 5 NHR 6 ;

SO 2 NR 5 NR 6 R 7 ;

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, aryl, or heterocyclyl;

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, straight, unsubstituted, and/or substituted and wherein the aryl, alkynyl, and heterocyclyl groups are substituted or unsubstituted.

25. The method according to claim 24 , wherein R 3 =hydrogen.

26. The method according to claim 24 , wherein R 4 =acetyl.

27. The method according to claim 24 , wherein X=OMe.

28. The method according to claim 24 , wherein R 3 =hydrogen, R 4 =acetyl, and X=OMe.

29. The method according to claim 24 , wherein R 2 =CH(O).

30. The method according to claim 24 , wherein R 2 =alkyl.

31. The method of claim 24 , wherein the mammal is human.

32. The method according to claim 24 , wherein the compound has the following chemical formula:

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

34. The method according to claim 24 , wherein the compound has the following chemical formula:

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

36. The method according to claim 24 , wherein the compound has the following chemical formula:

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

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

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

40. The method according to claim 24 , wherein the compound has the following chemical formula:

41. The method according to claim 24 , wherein the compound has the following chemical formula:

42. The compound method to claim 24 , wherein the compound has the following chemical formula:

43. The method according to claim 24 , wherein the compound has the following chemical formula:

Assignments (8)
CORRECTIVE ASSIGNMENT TO CORRECT THE INCORRECT PATENT NO. 7541537 PREVIOUSLY RECORDED AT REEL: 034045 FRAME: 0951. ASSIGNOR(S) HEREBY CONFIRMS THE SECURITY INTEREST. Recorded Aug 14, 2018
From: ALBANY MOLECULAR RESEARCH, INC.; ALO ACQUISITION LLC; AMRI BURLINGTON, INC.; AMRI RENSSELAER, INC.; CEDARBURG PHARMACEUTICALS, INC.; OSO BIOPHARMACEUTICALS MANUFACTURING, LLC
To: BARCLAYS BANK PLC, AS THE COLLATERAL AGENT
Reel/Frame 046796/0352 →
RELEASE OF SECURITY INTEREST Recorded Aug 31, 2017
From: BARCLAYS BANK PLC, AS COLLATERAL AGENT
To: ALBANY MOLECULAR RESEARCH, INC.; ALO ACQUISITION LLC; AMRI BURLINGTON, INC.; AMRI RENSSELAER, INC.; CEDARBURG PHARMACEUTICALS, INC.; OSO BIOPHARMACEUTICALS MANUFACTURING, LLC; AMRI SSCI, LLC; EUTICALS INC.
Reel/Frame 043742/0085 →
SECURITY INTEREST Recorded Oct 24, 2014
From: ALBANY MOLECULAR RESEARCH, INC.; ALO ACQUISITION LLC; AMRI BURLINGTON, INC.; AMRI RENSSELAER, INC.; CEDARBURG PHARMACEUTICALS, INC.; OSO BIOPHARMACEUTICALS MANUFACTURING, LLC
To: BARCLAYS BANK PLC, AS THE COLLATERAL AGENT
Reel/Frame 034045/0951 →
RELEASE OF SECURITY INTEREST Recorded Jul 9, 2014
From: WELLS FARGO
To: ALBANY MOLECULAR RESEARCH, INC.
Reel/Frame 033283/0357 →
SECURITY AGREEMENT Recorded Apr 20, 2012
From: ALBANY MOLECULAR RESEARCH, INC.; AMRI BURLINGTON, INC.; AMRI BOTHELL RESEARCH CENTER, INC.; AMRI RENESSELAER, INC.
To: WELLS FARGO BANK, NATIONAL ASSOCIATION
Reel/Frame 028078/0227 →
TERMINATION Recorded Apr 19, 2012
From: BANK OF AMERICA, N.A.
To: ALBANY MOLECULAR RESEARCH, INC.; AMRI BOTHELL RESEARCH CENTER, INC.; AMRI BURLINGTON, INC.; AMRI RENESSELAER, INC.
Reel/Frame 028072/0335 →
INTELLECTUAL PROPERTY SECURITY AGREEMENT Recorded Jun 6, 2011
From: ALBANY MOLECULAR RESEARCH, INC.; AMRI RENSSELAER, INC.; AMRI BOTHELL RESEARCH CENTER, INC.; AMRI BURLINGTON, INC.
To: BANK OF AMERICA, N.A., AS ADMINISTRATIVE AGENT
Reel/Frame 026397/0001 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 18, 2008
From: AMR TECHNOLOGY, INC.
To: ALBANY MOLECULAR RESEARCH, INC.
Reel/Frame 021998/0550 →