Anti-fibrotic pyridinones

1. A compound having the structure of formula (III):

or a pharmaceutically acceptable salt thereof, wherein

R 1 is selected from the group consisting of C 6-10 aryl optionally substituted with one or more R 4 , 5 to 9 membered heteroaryl optionally substituted with one or more R 4 , C 3-10 carbocyclyl optionally substituted with one or more R 4 , and 3-10 membered heterocyclyl optionally substituted with one or more R 4 ;

R 3 is selected from the group consisting of hydrogen, C 6-10 aryl, —(CH 2 ) n -(5-10 membered heteroaryl), —(CH 2 ) n —(C 3-10 carbocyclyl), and 3-10 membered heterocyclyl, each optionally substituted with one or more R 9 ;

ring A is selected from the group consisting of 5-6 membered heteroaryl, optionally substituted with one or more R 4 ;

each R 4 is independently selected from the group consisting of halogen, —CN, —OH, —C(O)R 8 , —SO 2 R 16 , optionally substituted C 1-6 alkyl, optionally substituted C 2-6 alkenyl, optionally substituted C 2-6 alkynyl, optionally substituted C 1-6 alkoxy, optionally substituted C 6-10 aryl optionally substituted with one or more R 11 , C 7-14 aralkyl optionally substituted with one or more R 11 , 5-10 membered heteroaryl optionally substituted with one or more R 11 , or independently two geminal R 4 together are oxo;

each R 9 is independently selected from the group consisting of hydroxy, halogen, optionally substituted C 1-6 alkyl, optionally substituted C 2-6 alkenyl, optionally substituted C 2-6 alkynyl, optionally substituted C 1-6 alkylthio, optionally substituted C 2-8 alkoxyalkyl, optionally substituted C 3-10 carbocyclyl, optionally substituted C 6-10 aryl, —OR 5 , —NR 14 R 15 , —C(O)R 8 , —SO 2 R 16 , —CN, and —NO 2 ;

or independently, two adjacent R 9 together with the atoms to which they are attached form an optionally substituted fused 5 to 6 membered heteroaryl or an optionally substituted fused 5 to 6 membered heterocyclyl;

R 14 is selected from the group consisting of hydrogen, optionally substituted C 1-6 alkyl, optionally substituted C 6-10 aryl, and —C(O)R 8 ;

R 15 is selected from the group consisting of hydrogen, optionally substituted C 1-6 alkyl, optionally substituted C 6-10 aryl, and —C(O)R 8 ;

each R 8 is independently selected from the group consisting of hydrogen, optionally substituted C 1-6 alkyl, optionally substituted C 2-6 alkenyl, optionally substituted C 2-6 alkynyl, C 6-10 aryl optionally substituted with one or more R 11 , C 7-14 aralkyl optionally substituted with one or more R 11 , —NR 12 R 13 , and —OR 5 ;

each R 12 is independently selected from the group consisting of hydrogen, optionally substituted C 1-6 alkyl, optionally substituted C 2-6 alkenyl, optionally substituted C 2-6 alkynyl, C 6-10 aryl optionally substituted with one or more R 11 , and C 7-14 aralkyl optionally substituted with one or more R 11 ;

each R 13 is independently selected from the group consisting of hydrogen, optionally substituted C 1-6 alkyl, optionally substituted C 2-6 alkenyl, optionally substituted C 2-6 alkynyl, C 6-10 aryl optionally substituted with one or more R 11 , and C 7-14 aralkyl optionally substituted with one or more R 11 ;

each R 5 is independently selected from the group consisting of hydrogen, optionally substituted C 1-6 alkyl, optionally substituted C 2-6 alkenyl, optionally substituted C 2-6 alkynyl, optionally substituted C 2-8 alkoxyalkyl, C 6-10 aryl optionally substituted with one or more R 11 , C 7-14 aralkyl optionally substituted with one or more R 11 , and —(CH 2 ) n —(3-10 membered heterocyclyl) optionally substituted with one or more R 10 ;

each R 10 is independently selected from the group consisting of optionally substituted C 1-6 alkyl, optionally substituted C 2-6 alkenyl, and optionally substituted C 2-6 alkynyl, or independently two geminal R 10 together are oxo;

each R 11 is independently selected from the group consisting of halogen, —CN, optionally substituted C 1-6 alkyl, optionally substituted C 2-6 alkenyl, optionally substituted C 2-6 alkynyl, and optionally substituted C 1-6 alkoxy;

each R 16 is independently selected from the group consisting of optionally substituted C 1-6 alkyl, optionally substituted C 2-6 alkenyl, optionally substituted C 2-6 alkynyl, C 6-10 aryl optionally substituted with one or more R 11 , C 7-14 aralkyl optionally substituted with one or more R 11 , —NR 12 R 13 , and —OR 5 ;

Z is selected from oxygen and sulfur;

each n is independently an integer from 0 to 4; and

the bonds represented by a solid and dashed line are independently selected from the group consisting of a single bond and a double bond, provided that

at least one of the hydrogen atoms of R 1 or R 3 is deuterium.

2. The compound of claim 1 , wherein

R 3 is selected from the group consisting of C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 carbocyclyl, and 3-10 membered heterocyclyl, each optionally substituted with one or more R 9 .

3. The compound of claim 1 , wherein R 1 is selected from C 6-10 aryl optionally substituted with one or more R 4 , or 5 to 9 membered heteroaryl optionally substituted with one or more R 4 .

4. The compound of claim 2 , wherein at least one of the hydrogen atoms of R 1 is deuterium.

5. The compound of claim 2 , wherein R 1 is 5 to 6 membered heteroaryl optionally substituted with one or more R 4 .

6. The compound of claim 5 , wherein R 1 is pyridazinyl optionally substituted with one or more R 4 .

7. The compound of claim 5 , wherein R 1 is pyrazolyl or 1-methyl pyrazolyl optionally substituted with one or more R 4 .

8. The compound of claim 7 , wherein R 1 is 1-CD 3 pyrazolyl.

9. The compound of claim 1 , wherein R 3 is hydrogen.

10. The compound of claim 1 , wherein R 3 is selected from C 6-10 aryl optionally substituted with one or more R 9 .

11. The compound of claim 10 , wherein R 3 is phenyl, optionally substituted with one or more R 9 .

12. The compound of claim 10 , wherein R 3 is unsubstituted.

13. The compound of claim 10 , wherein R 9 is selected from cyano, halogen, optionally substituted C 1-6 alkyl, or optionally substituted C 1-6 alkoxy.

14. The compound of claim 13 , wherein R 9 is selected from cyano, fluoro, chloro, methyl, ethyl, ethoxy, methoxy, trifluoromethyl, trifluoromethoxy or difluoromethoxy.

15. The compound of claim 10 , wherein two adjacent R 9 together with the carbon atoms to which they are attached to form an optionally substituted fused 5 to 6 membered heteroaryl.

16. The compound of claim 15 , wherein the 5 to 6 membered heteroaryl is selected from imidazolyl or oxazolyl.

17. The compound of claim 1 , wherein ring A is selected from 5-membered heteroaryl or 6-membered heteroaryl, each optionally substituted with one or more R 4 .

18. The compound of claim 1 , wherein at least one hydrogen atom of ring A is deuterium.

19. The compound of claim 17 , wherein ring A is selected from

each optionally substituted with one or more R 4 ; and wherein each R 17 is independently selected from hydrogen, optionally substituted C 1-6 alkyl, optionally substituted C 3-6 cycloalkyl, optionally substituted C 2-8 alkoxyalkyl, optionally substituted C-carboxy, acyl, C 6-10 aryl optionally substituted with one or more R 11 , or C 7-14 aralkyl optionally substituted with one or more R 11 .

20. The compound of claim 19 , wherein ring A is selected from

each optionally substituted with one or more R 4 .

21. The compound of claim 18 , wherein ring A is selected from

each optionally substituted with one or more R 4 .

22. The compound of claim 19 , wherein R 17 is selected from hydrogen, methyl, ethyl, isopropyl, cyclopropyl, —(CH 2 ) 2 F, —(CH 2 ) 2 OH, —(CH 2 ) 2 OCH 3 , —(CH 2 ) 2 OC 2 H 5 , —(CH 2 ) 2 OC 3 H 7 , —C(O)O-t-Bu, —C(O)CH 3 or benzyl, and wherein one of the hydrogen is deuterium.

23. The compound of claim 18 , wherein ring A is selected from

and wherein each R 17 is —CD 3 .

24. The compound of claim 1 , wherein R 4 is selected from halogen, optionally substituted C 1-6 alkyl, or C 7-14 aralkyl optionally substituted with one or more R 11 , or two geminal R 4 together are oxo.

25. The compound of claim 24 , wherein R 4 is selected from fluoro, methyl, trifluoromethyl, —(CH 2 ) 2 OH, benzyl, or two geminal R 4 together are oxo.

26. The compound of claim 17 , wherein ring A is unsubstituted.

27. The compound of claim 1 , wherein Z is oxygen.

28. The compound of claim 1 , wherein the bonds represented by a solid and dashed line are double bonds, provided that when ring A is

one of the bonds represented by a solid and dashed line is a single bond.

29. The compound of claim 1 , wherein the compound is selected from Compound 724 of Table 1, or a pharmaceutically acceptable salt thereof.

30. A pharmaceutical composition comprising an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, diluent, excipient or combination thereof.

31. A method of treating a fibrotic condition, comprising administering a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof.