Compositions and methods for treating cancer
View Patent ↗Provided herein are methods of treating cancer comprising administering decitabine in combination with compounds that inhibit the deamination enzyme responsible for the inactivation of decitabine.
1. A composition comprising decitabine and a compound of formula I:
wherein:
one of R 1 and R 2 is F, and the other is selected from H and F;
one of R 3 and R 4 is H, and the other is selected from H and OH;
where ------- is a covalent bond or absent, and R 4 is absent when ------- is a covalent bond;
or a pharmaceutically acceptable salt, a C 1-6 alkyl ester, or a C 2-6 alkenyl ester thereof.
2. The composition of claim 1 , wherein R 1 and R 2 are each F.
3. The composition of claim 2 , wherein said compound of formula I is a compound of formula II:
or a pharmaceutically acceptable salt, a C 1-6 alkyl ester, or a C 2-6 alkenyl ester thereof.
4. The composition of claim 3 wherein said compound of formula II is a compound of formula VIII:
or a pharmaceutically acceptable salt, a C 1-6 alkyl ester, or a C 2-6 alkenyl ester thereof.
5. The composition of claim 4 wherein said compound is a compound of formula VIII:
6. The composition of claim 2 , wherein said compound of formula I is a compound of formula III:
wherein:
one of R 3 and R 4 is H, and the other is selected from H and OH;
or a pharmaceutically acceptable salt, a C 1-6 alkyl ester, or a C 2-6 alkenyl ester thereof.
7. The composition of claim 1 , wherein said compound of formula I is a compound of formula IV:
or a pharmaceutically acceptable salt, a C 1-6 alkyl ester, or a C 2-6 alkenyl ester thereof.
8. The composition of claim 7 , wherein said compound of formula IV is a compound of formula V:
or a pharmaceutically acceptable salt, a C 1-6 alkyl ester, or a C 2-6 alkenyl ester thereof.
9. The composition of claim 1 , wherein said compound of formula I is a compound of formula VI:
or a pharmaceutically acceptable salt, a C 1-6 alkyl ester, or a C 2-6 alkenyl ester thereof.
10. The composition of claim 9 , wherein said compound of formula VI is a compound of formula VII:
or a pharmaceutically acceptable salt, a C 1-6 alkyl ester, or a C 2-6 alkenyl ester thereof.
11. A method of treating a cancer being treated with responsive to decitabine comprising:
administering to a subject a composition comprising decitabine; and administering to a subject a composition comprising a compound of formula I:
wherein:
one of R 1 and R 2 is F, and the other is selected from H and F;
one of R 3 and R 4 is H, and the other is selected from H and OH;
where is a covalent bond or absent, and R 4 is absent when is a covalent bond;
or a pharmaceutically acceptable salt, a C 1-6 alkyl ester, or a C 2-6 alkenyl ester thereof.
12. The method of claim 11 , wherein said cancer is selected from the group consisting of hematological cancers and solid cancers.
13. The method of claim 12 , wherein said cancer is a hematological cancer selected from the group consisting of myelodysplastic syndrome, acute myeloid leukemia and chronic myeloid leukemia.
14. The method of claim 12 , where the cancer is a solid cancer selected from the group consisting of pancreatic cancer, ovarian cancer, peritoneal cancer, non small cell lung cancer, and metastatic breast cancer.
15. The method of claim 11 , wherein the compound is a compound of formula VIII:
or a pharmaceutically acceptable salt, a C 1-6 alkyl ester, or a C 2-6 alkenyl ester thereof.
16. A pharmaceutical composition comprising
(i) decitabine;
(ii) a compound of formula I:
wherein:
one of R 1 and R 2 is F, and the other is selected from H and F;
one of R 3 and R 4 is H, and the other is selected from H and OH;
where is a covalent bond or absent, and R 4 is absent when is a covalent bond;
or a pharmaceutically acceptable salt, a C 1-6 alkyl ester, or a C 2-6 alkenyl ester thereof; and
(iii) a pharmaceutically acceptable excipient.
17. The pharmaceutical composition of claim 16 , wherein R 1 and R 2 are each F.
18. A pharmaceutical composition of claim 16 wherein the compound of formula I compound is a compound of formula VIII:
or a pharmaceutically acceptable salt, a C 1-6 alkyl ester, or a C 2-6 alkenyl ester thereof; and a pharmaceutically acceptable excipient.
19. The method according to claim 11 , wherein the composition comprising decitabine and the composition comprising a compound of formula I are simultaneously administered.
20. The method according to claim 11 , wherein the composition comprising decitabine and the composition comprising a compound of formula I are sequentially administered.
21. The method of claim 13 , wherein said hematological cancer is a myelodysplastic syndrome.