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. A pharmaceutical composition comprising a compound of claim 1 .
4. A method for preparing a compound of claim 1 comprising reacting a betulic acid halide protected by a substituent R 1 , the substituent R 1 further defined as a protected hydroxy group or amino group, with an alcohol or amine appropriately substituted to provide the substituent R 2 .
5. The method of claim 4 , further comprising deprotecting the protected hydroxy or amino group at R 1 to provide a compound of formula (I) wherein R 1 is a hydroxy or amino group.
6. A method of treating a melanoma or neuroectodermal tumor in a mammal comprising administering to the mammal a compound of claim 1 .
7. A method of treating a sarcoma in a mammal comprising administering to the mammal a compound of claim 1 .
8. The method of claim 6 , further comprising administering to the mammal at least one other substance, further defined as a cytostatically active substance and/or cell-death-modulating substance.
9. The method of claim 8 , wherein the other substance is an antisense oligonucleotide against an anti-apoptotic Bcl-2 family member or Mcl-1.
10. The method of claim 9 , wherein the other substance is Bcl-2 or Bcl-xL.