- Document Number:
20110319365
- Appl. No:
13/202833
- Application Filed:
February 24, 2010
- نبذة مختصرة :
The present disclosure concerns complexes of 4-hydroperoxy ifosfamide. In one embodiment the complexes can be represented by the formula [chemical expression included] wherein A represents an ammonium species selected from the conjugate acid of a basic amino acid, quaternary ammonium, aliphatic ammonium, heterocyclic ammonium, aromatic ammonium, substituted and unsubstituted pyridinium, guanidinium, and amidinium, and wherein X and Y independently represent leaving groups. Also disclosed herein are methods for making such compounds and formulating pharmaceutical compositions thereof. Methods for administering the disclosed compounds to subjects, particularly to treat hyperproliferative disorders, also are disclosed.
- Inventors:
Morgan, Lee Roy (New Orleans, LA, US)
- Claim:
1. A compound of the formula: [chemical expression included] wherein A represents an ammonium species selected from the conjugate acid of a basic amino acid selected from lysine, arginine, histidine, homolysine, homoarginine, and ornithine; quaternary ammonium; aliphatic ammonium; heterocyclic ammonium; aromatic ammonium; substituted and unsubstituted pyridinium; guanidinium; and amidinium; and wherein X and Y independently represent leaving groups.
- Claim:
2. The compound of claim 1, wherein A is the conjugate acid of a basic amino acid.
- Claim:
3. (canceled)
- Claim:
4. The compound of claim 1, wherein A represents BH+ and B is an amine selected from the basic amino acids, cyclohexylamine, pyridine, N,N-dimethylaminopyridine, diazabicyclononane, diazabicycloundecene, N-methyl-N-ethylamine, diethylamine, triethylamine, diisopropylethylamine, mono-, bis- or tris-(2-hydroxyethyl)amine, 2-hydroxy-tert-butylamine, tris(hydroxymethyl)methylamine, N,N-dimethyl-N-(2-hydroxyethyl)amine, tri-(2-hydroxyethyl)amine and N-methyl-D-glucamine.
- Claim:
5. The compound of claim 4, wherein B is a basic amino acid selected from lysine, homolysine, arginine, homoarginine, histidine, ornithine, and combinations or two or more thereof.
- Claim:
6. The compound of claim 5, wherein B is lysine.
- Claim:
7. The compound of claim 1, wherein X and Y independently are selected from the halogens and the sulfonates.
- Claim:
8. The compound of claim 7, wherein X and Y are halogen.
- Claim:
9. The compound of claim 8, wherein X and Y are chlorine.
- Claim:
10. A pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable carrier.
- Claim:
11-15. (canceled)
- Claim:
16. The pharmaceutical composition of claim 10, wherein the composition comprises a solution formulated for administration to a human subject.
- Claim:
17. The pharmaceutical composition of claim 16, wherein the solution comprises from about 0.1 mg/ml to about 250 mg/ml of the compound.
- Claim:
18-19. (canceled)
- Claim:
20. A complex comprising a 4-hydroperoxy ifosfamide anion and an ammonium cation.
- Claim:
21. The complex of claim 20, further comprising a second amine or ammonium cation.
- Claim:
22. The complex of claim 21, wherein the ammonium cation is a conjugate acid of lysine or tris(hydroxymethyl)methylamine.
- Claim:
23. A pharmaceutical composition comprising the complex of claim 20 and a pharmaceutically acceptable carrier.
- Claim:
24. The pharmaceutical composition of claim 23, wherein the composition comprises at least two equivalents of amine base per equivalent of 4-hydroperoxy ifosfamide.
- Claim:
25. A method of treating a subject with a tumor, comprising administering a therapeutically effective amount of the pharmaceutical composition of claim 10 to the subject having a tumor, wherein the composition comprises a therapeutically effective amount of the compound.
- Claim:
26. The method of claim 25, wherein the subject has a central nervous system tumor, breast cancer, bone cancer, lung cancer, melanoma, ovarian cancer or leukemia.
- Claim:
27. The method of claim 25, comprising administering from about 10 mg/m2/day to about 700 mg/m2/day of the compound to the subject.
- Claim:
28-30. (canceled)
- Claim:
31. The method of claim 26, wherein the central nervous system tumor comprises glioblastoma, astrocytoma, oligodendroglioma, or ependymoblastoma.
- Claim:
32. The method of claim 31, wherein the central nervous system tumor comprises a primary brain tumor or a metastatic brain tumor.
- Claim:
33. A lyophilisate comprising 4-hydroperoxy ifosfamide, having a structure of formula: [chemical expression included] wherein A represents an ammonium species selected from the conjugate acid of a basic amino acid, quaternary ammonium, aliphatic ammonium, heterocyclic ammonium, aromatic ammonium, substituted and unsubstituted pyridinium, guanidinium, and amidinium; and wherein X and Y independently represent leaving groups.
- Claim:
34. The lyophilisate of claim 33, wherein X and Y are chloride.
- Claim:
35. The lyophilisate of claim 33, wherein the basic amino acid is lysine.
- Claim:
36. The lyophilisate of claim 33, further comprising an excipient.
- Current U.S. Class:
514/110
- Current International Class:
61; 61; 61; 07
- الرقم المعرف:
edspap.20110319365
Processing Request
No Comments.