Compositions and methods for treating cancer
View Patent ↗Provided herein are compounds used to inhibit the deamination enzyme responsible for the inactivation of therapeutic compounds, and methods of using them.
1. The 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 compound of claim 1 , wherein R 1 and R 2 are each F.
3. The compound 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 compound of claim 1 wherein said compound of formula I 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 compound of formula VIII:
6. The compound 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 compound 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 compound 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 compound of claim 1 , wherein said compound of formula I is a compound of formula VI:
or a pharmaceutically acceptable salt, a alkyl ester, or a C 2-6 alkenyl ester thereof.
10. The compound 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 pharmaceutical 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;
and a pharmaceutically acceptable excipient.
12. The pharmaceutical composition of claim 11 , wherein R 1 and R 2 are each F.
13. The pharmaceutical composition of claim 12 , 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.
14. The pharmaceutical composition of claim 11 , wherein the compound of formula I 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.
15. The pharmaceutical composition of claim 14 , wherein the compound is a compound of formula VIII:
16. The pharmaceutical composition of claim 12 , 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.
17. The pharmaceutical composition of claim 11 , 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.
18. The pharmaceutical composition of claim 17 , 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.
19. The pharmaceutical composition of claim 11 , 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.
20. The pharmaceutical composition of claim 19 , 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.