Compounds for use in treatment of mucositis
The present invention provides methods for treating and/or preventing mucostitis with one or more compounds, or pharmaceutically acceptable salts thereof, disclosed herein, or compositions comprising the same.
1. A method of treating mucositis in a mammal comprising administering to the mammal in need thereof a therapeutically effective amount of a compound of Formula III:
or a pharmaceutically acceptable salt thereof,
wherein:
each A is, independently, —C═O, —C═S, or CH 2 ;
each D is, independently, O or S;
each R 1 is, independently, hydrogen, C 1-3 alkyl, C 1-3 alkoxy, halo, or haloC 1-3 alkyl;
each R 2 is, independently, hydrogen, C 1-3 alkyl, C 1-3 alkoxy, halo, or haloC 1-3 alkyl;
each R 3 is, independently, hydrogen, C 1-4 alkyl, C 1-4 alkoxy, halo, or haloC 1-4 alkyl; and
each R 4 is, independently, hydrogen, C 1-3 alkyl, C 1-3 alkoxy, halo, or haloC 1-3 alkyl.
2. The method of claim 1 wherein at least one A is —C═O.
3. The method of claim 1 wherein at least one D is O.
4. The method of claim 1 wherein each R 1 is, independently, hydrogen, methyl, methoxy, halo, or haloC 1-3 alkyl.
5. The method of claim 1 wherein at least one R 1 is hydrogen.
6. The method of claim 1 wherein each R 2 is, independently, hydrogen, methyl, methoxy, or halo.
7. The method of claim 1 wherein at least one R 2 is hydrogen.
8. The method of claim 1 wherein each R 3 is, independently, methyl, methoxy, halo, or haloC 1-3 alkyl.
9. The method of claim 1 wherein each R 3 is, independently, haloC 1-3 alkyl.
10. The method of claim 1 wherein at least one R 3 is trifluoromethyl.
11. The method of claim 1 wherein each R 4 is, independently, hydrogen, methyl, methoxy, halo, or haloC 1-3 alkyl.
12. The method of claim 1 wherein each R 4 is, independently, hydrogen, methyl, methoxy, or halo.
13. The method of claim 1 wherein at least one R 4 is hydrogen.
14. The method of claim 1 wherein:
each A is, independently, —C═O or —C═S;
each D is, independently, O or S;
each R 1 is, independently, hydrogen, methyl, methoxy, halo, or halomethyl;
each R 2 is, independently, hydrogen, halo, or halomethyl;
each R 3 is, independently, methyl, ethyl, methoxy, ethoxy, halo, halomethyl, or haloethyl; and
each R 4 is, independently, hydrogen, methyl, ethyl, methoxy, ethoxy, halo, halomethyl, or haloethyl.
15. The method of claim 1 wherein:
each A is —C═O;
each D is O;
each R 1 is, independently, hydrogen, halo, or halomethyl;
each R 2 is, independently, hydrogen or halo;
each R 3 is, independently, methyl, methoxy, halo, or halomethyl; and
each R 4 is, independently, hydrogen, methyl, methoxy, halo, or halomethyl.
16. The method of claim 1 wherein:
each A is —C═O;
each D is O;
each R 1 is, independently, hydrogen or halo;
each R 2 is, independently, hydrogen or halo;
each R 3 is, independently, methyl, halo, or halomethyl; and
each R 4 is, independently, hydrogen, methyl, halo, or halomethyl.
17. The method of claim 1 wherein:
each A is —C═O;
each D is O;
each R 1 is, independently, hydrogen or halo;
each R 2 is, independently, hydrogen or halo;
each R 3 is, independently, methyl, halo, or halomethyl; and
each R 4 is, independently, hydrogen, methyl, halo, or halomethyl.
18. The method of claim 1 wherein:
each A is —C═O;
each D is O;
each R 1 is, independently, hydrogen or halo;
each R 2 is, independently, hydrogen or halo;
each R 3 is, independently, halo or halomethyl; and
each R 4 is, independently, hydrogen, halo, or halomethyl.
19. The method according to claim 1 wherein the compound of Formula III is,
or a pharmaceutically acceptable salt thereof.
20. The method of claim 1 wherein the mammal is a human.
21. The method of claim 1 wherein the compound of Formula III is present in a composition further comprising palifermin.
22. A composition comprising
or a pharmaceutically acceptable salt thereof, and palifermin.