Methods and compositions for inhibiting tumor growth
The present invention relates to novel betulinic acid derivatives with increased activity for the treatment of carcinomas and HIV diseases, a method for preparing such novel betulinic acid derivatives as well as their use as pharmaceuticals.
1. A betulinic acid derivative, salt, or inclusion compound having a formula (I):
wherein R 1 is a hydroxy group, an amino group, a protected hydroxy group, or a protected amino group; and
R 2 is one of:
2. The compound of claim 1 , wherein R 1 is one of the following:
3. The compound of claim 1 , wherein the compound has the formula:
4. The compound of claim 1 , wherein the compound has the formula:
5. A pharmaceutical composition comprising a compound of claim 1 .
6. A method of treating cancer in a mammal comprising administering to the mammal an effective amount of a betulinic acid derivative, salt, or inclusion compound having a formula (I):
wherein R 1 is a hydroxy group, an amino group, a protected hydroxy group, or a protected amino group; and
R 2 is one of:
wherein the cancer in the mammal is treated.
7. The method of claim 6 , wherein R 1 is one of the following:
8. The method of claim 6 , wherein the cancer is a squamous carcinoma.
9. The method of claim 6 , further comprising administering to the mammal a cytostatically active substance and/or a cell-death-modulating substance.
10. The method of claim 9 , wherein the cell-death-modulating substance is an antisense oligonucleotide against an anti-apoptotic Bcl-2 family member or Mcl-1.
11. The method of claim 10 , wherein the Bcl-2 family member is Bcl-2 or Bcl-xL.
12. A method of treating HIV disease in a mammal comprising administering to the mammal an effective amount of a betulinic acid derivative, salt, or inclusion compound having a formula (I):
wherein R 1 is a hydroxy group, an amino group, a protected hydroxy group, or a protected amino group; and
R 2 is one of:
wherein the cancer in the mammal is treated.
13. The method of claim 12 , wherein R 1 is one of the following:
14. The method of claim 6 , wherein R 2 is:
15. The method of claim 6 , wherein R 2 is:
16. The method of claim 12 , wherein R 2 is:
17. The method of claim 12 , wherein R 2 is:
18. The method of claim 12 , wherein the compound has the formula:
19. The method of claim 12 , wherein the compound has the formula: