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 C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 carbocyclyl, and 3-10 membered heterocyclyl, each substituted with at least two adjacent R 9 ;

said 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; and wherein R 3 is further optionally substituted with additional one or more R 9 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 ;

ring A is a 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;

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.

2. The compound of claim 1 , wherein R 3 is selected from the group consisting of C 6-10 aryl or 5-10 membered heteroaryl.

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 3 , wherein R 1 is phenyl optionally substituted with one or more R 4 .

5. The compound of claim 3 , wherein R 1 is 9 membered heteroaryl optionally substituted with one or more R 4 .

6. The compound of claim 5 , wherein R 1 is imidazo[1,2-a]pyridin-yl.

7. The compound of claim 3 , wherein R 1 is selected from pyridyl or pyridazinyl optionally substituted with one or more R 4 .

8. The compound of claim 3 , wherein R 1 is pyrazolyl or 1-methyl pyrazolyl optionally substituted with one or more R 4 .

9. The compound of claim 4 , wherein R 3 is phenyl 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.

10. The compound of claim 9 , wherein the 5 to 6 membered heteroaryl is selected from imidazolyl or oxazolyl.

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

12. The compound of claim 11 , 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 .

13. The compound of claim 12 , wherein ring A is selected from:

each optionally substituted with one or more R 4 .

14. The compound of claim 12 , 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.

15. 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.

16. The compound of claim 15 , wherein R 4 is selected from fluoro, methyl, trifluoromethyl, —(CH 2 ) 2 OH, benzyl, or two geminal R 4 together are oxo.

17. The compound of claim 12 , wherein ring A is unsubstituted.

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

19. The compound of claim 1 , wherein the compound is selected from the group consisting of Compounds 727, 728, 733, 734, 737 and 738 of Table 1.

or a pharmaceutically acceptable salt thereof.

20. 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.