Aldose reductase inhibitors and methods of use thereof
View Patent ↗The present disclosure relates to novel compounds and pharmaceutical compositions thereof, and methods for promoting healthy aging of skin, the treatment of skin disorders, the treatment of cardiovascular disorders, the treatment of renal disorders, the treatment of angiogenesis disorders, such as cancer, treatment of tissue damage, such as non-cardiac tissue damage, the treatment of evolving myocardial infarction, the treatment of ischemic injury, and the treatment of various other disorders, such as complications arising from diabetes with the compounds and compositions of the invention. Other disorders can include, but are not limited to, atherosclerosis, coronary artery disease, diabetic nephropathy, diabetic neuropathy, diabetic retinopathy, diabetic cardiomyopathy, infections of the skin, peripheral vascular disease, stroke, asthma, and the like.
1. A compound of Formula (I)
wherein,
R 1 is CO 2 R 2 ;
R 2 is H, (C 1 -C 6 )-alkyl, (C 1 -C 6 )-hydroxyalkyl, or (C 1 -C 6 )-aminoalkyl;
X 1 is H;
X 2 is H;
Y is C═O;
Z is
A 1 is S;
A 2 is N; and
R 3 through R 6 are independently hydrogen, halogen, cyano, acyl, haloalkyl, haloalkoxy, haloalkylthio, trifluoroacetyl, (C 1 -C 4 )-alkyl, (C 1 -C 4 )-alkoxy, (C 1 -C 4 )-alkylthio, (C 1 -C 4 )-alkylsulfinyl, or (C 1 -C 4 )-alkyl sulfonyl;
or a pharmaceutically acceptable salt or solvate thereof.
2. The compound of claim 1 , wherein R 2 is (C 1 -C 6 )-alkyl.
3. The compound of claim 2 , wherein R 3 through R 6 are independently hydrogen, halogen, or haloalkyl.
4. The compound of claim 1 , wherein R 1 is (C 1 -C 6 )-hydroxyalkyl.
5. The compound of claim 4 , wherein R 3 through R 6 are independently hydrogen, halogen, or haloalkyl.
6. The compound of claim 1 , wherein R 1 is (C 1 -C 6 )-aminoalkyl.
7. The compound of claim 6 , wherein R 3 through R 6 are independently hydrogen, halogen, or haloalkyl.
8. The compound of claim 1 , wherein R 2 is H.
9. The compound of claim 8 , wherein R 3 through R 6 are independently hydrogen, halogen, or haloalkyl.
10. The compound of claim 1 , wherein R 3 , R 5 and R 6 are each hydrogen; and R 4 is hydrogen, halogen, or haloalkyl.
11. The compound of claim 2 , wherein R 3 , R 5 and R 6 are each hydrogen; and R 4 is hydrogen, halogen, or haloalkyl.
12. The compound of claim 4 , wherein R 3 , R 5 and R 6 are each hydrogen; and R 4 is hydrogen, halogen, or haloalkyl.
13. The compound of claim 6 , wherein R 3 , R 5 and R 6 are each hydrogen; and R 4 is hydrogen, halogen, or haloalkyl.
14. The compound of claim 8 , wherein R 3 , R 5 and R 6 are each hydrogen; and R 4 is hydrogen, halogen, or haloalkyl.
15. The compound
or a pharmaceutically acceptable salt or solvate thereof.
16. The compound
or a pharmaceutically acceptable salt or solvate thereof.
17. The compound
or a pharmaceutically acceptable salt or solvate thereof.
18. The compound
or a pharmaceutically acceptable salt or solvate thereof.
19. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.
20. A pharmaceutical composition comprising a compound of claim 15 and a pharmaceutically acceptable carrier.
21. A pharmaceutical composition comprising a compound of claim 16 and a pharmaceutically acceptable carrier.
22. A pharmaceutical composition comprising a compound of claim 17 and a pharmaceutically acceptable carrier.
23. A pharmaceutical composition comprising a compound of claim 18 and a pharmaceutically acceptable carrier.