Granted Patent B2

US 8,343,952 · App. 12/860,073 · Granted Jan 1, 2013

Abstract

Claims (175)

1. A compound having the formula:

wherein R 2 is chosen from:

i) —OR 6 ; or

ii) —NR 7a R 7b ;

R 6 is hydrogen, methyl, or ethyl;

R 7a and R 7b are each independently:

i) hydrogen; or

ii) methyl;

R 3 is hydrogen or methyl;

R 8a and R 8b are each independently hydrogen, methyl, or ethyl;

R 10 represents from 1 to 5 substitutions for hydrogen, said substitutions independently chosen from:

i) fluoro;

ii) chloro;

iii) trifluoromethyl;

iv) methyl; or

v) two adjacent R 10 units can be taken together to form a 6-member ring having one or two oxygen atoms, provided no two oxygen atoms are adjacent to one another in the ring; and

pharmaceutically acceptable salts thereof.

2. The compound according to claim 1 , having the formula:

3. The compound according to claim 2 , wherein R 2 is —OH.

4. The compound according to claim 2 , wherein R 2 is —OCH 3 or —OCH 2 CH 3 .

5. The compound according to claim 2 , wherein R 2 is chosen from —NH 2 , —NHCH 3 , or —N(CH 3 ) 2 .

6. The compound according to claim 2 , wherein R 8a and R 8b are both hydrogen.

7. The compound according to claim 1 , having the formula:

8. The compound according to claim 7 , wherein R 2 is —OH.

9. The compound according to claim 7 , wherein R 2 is —OCH 3 or —OCH 2 CH 3 .

10. The compound according to claim 7 , wherein R 2 is chosen from —NH 2 , —NHCH 3 , or —N(CH 3 ) 2 .

11. The compound according to claim 7 , wherein R 8a and R 8b are both hydrogen.

12. The compound according to claim 1 , having the formula:

13. The compound according to claim 12 , wherein R 2 is —OH.

14. The compound according to claim 12 , wherein R 2 is —OCH 3 or —OCH 2 CH 3 .

15. The compound according to claim 12 , wherein R 2 is chosen from —NH 2 , —NHCH 3 , or —N(CH 3 ) 2 .

16. The compound according to claim 12 , wherein R 8a and R 8b are both hydrogen.

17. The compound according to claim 1 , having the formula:

18. The compound according to claim 17 , wherein R 2 is —OH.

19. The compound according to claim 17 , wherein R 2 is —OCH 3 or —OCH 2 CH 3 .

20. The compound according to claim 17 , wherein R 2 is chosen from —NH 2 , —NHCH 3 , or —N(CH 3 ) 2 .

21. The compound according to claim 17 , wherein R 8a and R 8b are both hydrogen.

22. The compound according to claim 1 , having the formula:

23. The compound according to claim 22 , wherein R 2 is —OH.

24. The compound according to claim 22 , wherein R 2 is —OCH 3 or —OCH 2 CH 3 .

25. The compound according to claim 22 , wherein R 2 is chosen from —NH 2 , —NHCH 3 , or —N(CH 3 ) 2 .

26. The compound according to claim 22 , wherein R 8a and R 8b are both hydrogen.

27. A compound chosen from:

{[5-(3-Chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid;

{[5-(3-Chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid methyl ester;

{[5-(3-Chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid ethyl ester;

5-(3-Chlorophenyl)-N-(2-amino-2-oxoethyl)-3-hydroxylpyridin-2-yl amide;

5-(3-Chlorophenyl)-N-(2-methylamino-2-oxoethyl)-3-hydroxylpyridin-2-yl amide;

5-(3-Chlorophenyl)-N-(2-dimethylamino-2-oxoethyl)-3-hydroxylpyridin-2-yl amide;

{[5-(3-Chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}-2-methylacetic acid;

{[5-(3-Chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}-2-methylacetic acid methyl ester;

{[5-(3-Chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}-2-methylacetic acid ethyl ester;

5-(3-Chlorophenyl)-N-(1-methyl-2-amino-2-oxoethyl)-3-hydroxylpyridin-2-yl amide;

5-(3-Chlorophenyl)-N-(1-methyl-2-methylamino-2-oxoethyl)-3-hydroxylpyridin-2-yl amide;

5-(3-Chlorophenyl)-N-(1-methyl-2-dimethylamino-2-oxoethyl)-3-hydroxylpyridin-2-yl amide;

{[5-(3-Chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}-2,2-dimethylacetic acid;

{[5-(3-Chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}-2,2-dimethylacetic acid methyl ester;

{[5-(3-Chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}-2,2-dimethylacetic acid ethyl ester;

5-(3-Chlorophenyl)-N-(1,1-dimethyl-2-amino-2-oxoethyl)-3-hydroxylpyridin-2-yl amide;

5-(3-Chlorophenyl)-N-(1,1-dimethyl-2-methylamino-2-oxoethyl)-3-hydroxylpyridin-2-yl amide;

5-(3-Chlorophenyl)-N-(1,1-dimethyl-2-dimethylamino-2-oxoethyl)-3-hydroxylpyridin-2-yl amide;

{[5-(4-Fluorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid;

{[5-(4-Fluorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid methyl ester;

{[5-(4-Fluorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid ethyl ester;

5-(4-Fluorophenyl)-N-(2-amino-2-oxoethyl)-3-hydroxylpyridin-2-yl amide;

5-(3-Fluorophenyl)-N-(2-methylamino-2-oxoethyl)-3-hydroxylpyridin-2-yl amide;

5-(4-Fluorophenyl)-N-(2-dimethylamino-2-oxoethyl)-3-hydroxylpyridin-2-yl amide;

{[5-(4-Fluorophenyl)-3-hydroxypyridine-2-carbonyl]amino}-2-methylacetic acid;

{[5-(4-Fluorophenyl)-3-hydroxypyridine-2-carbonyl]amino}-2-methylacetic acid methyl ester;

{[5-(4-Fluorophenyl)-3-hydroxypyridine-2-carbonyl]amino}-2-methylacetic acid ethyl ester;

5-(4-Fluorophenyl)-N-(1-methyl-2-amino-2-oxoethyl)-3-hydroxylpyridin-2-yl amide;

5-(4-Fluorophenyl)-N-(1-methyl-2-methylamino-2-oxoethyl)-3-hydroxylpyridin-2-yl amide;

5-(4-Fluorophenyl)-N-(1-methyl-2-dimethylamino-2-oxoethyl)-3-hydroxylpyridin-2-yl amide;

{[5-(4-Fluorophenyl)-3-hydroxypyridine-2-carbonyl]amino}-2,2-dimethylacetic acid;

{[5-(4-Fluorophenyl)-3-hydroxypyridine-2-carbonyl]amino}-2,2-dimethylacetic acid methyl ester;

{[5-(4-Fluorophenyl)-3-hydroxypyridine-2-carbonyl]amino}-2,2-dimethylacetic acid ethyl ester;

5-(4-Fluorophenyl)-N-(1,1-dimethyl-2-amino-2-oxoethyl)-3-hydroxylpyridin-2-yl amide;

5-(4-Fluorophenyl)-N-(1,1-dimethyl-2-methylamino-2-oxoethyl)-3-hydroxylpyridin-2-yl amide;

5-(4-Fluorophenyl)-N-(1,1-dimethyl-2-dimethylamino-2-oxoethyl)-3-hydroxylpyridin-2-yl amide;

{[5-(3-Trifluoromethylphenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid;

{[5-(3-Trifluoromethylphenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid methyl ester;

{[5-(3-Trifluoromethylphenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid ethyl ester;

5-(3-Trifluoromethylphenyl)-N-(2-amino-2-oxoethyl)-3-hydroxylpyridin-2-yl amide;

5-(3-Trifluoromethylphenyl)-N-(2-methylamino-2-oxoethyl)-3-hydroxylpyridin-2-yl amide;

5-(3-Trifluoromethylphenyl)-N-(2-dimethylamino-2-oxoethyl)-3-hydroxylpyridin-2-yl amide;

{[5-(3-Trifluoromethylphenyl)-3-hydroxypyridine-2-carbonyl]amino}-2-methylacetic acid;

{[5-(3-Trifluoromethylphenyl)-3-hydroxypyridine-2-carbonyl]amino}-2-methylacetic acid methyl ester;

{[5-(3-Trifluoromethylphenyl)-3-hydroxypyridine-2-carbonyl]amino}-2-methylacetic acid ethyl ester;

5-(3-Trifluoromethylphenyl)-N-(1-methyl-2-amino-2-oxoethyl)-3-hydroxylpyridin-2-yl amide;

5-(3-Trifluoromethylphenyl)-N-(1-methyl-2-methylamino-2-oxoethyl)-3-hydroxylpyridin-2-yl amide;

5-(3-Trifluoromethylphenyl)-N-(1-methyl-2-dimethylamino-2-oxoethyl)-3-hydroxylpyridin-2-yl amide;

{[5-(3-Trifluoromethylphenyl)-3-hydroxypyridine-2-carbonyl]amino}-2,2-dimethylacetic acid;

{[5-(3-Trifluoromethylphenyl)-3-hydroxypyridine-2-carbonyl]amino}-2,2-dimethylacetic acid methyl ester;

{[5-(3-Trifluoromethylphenyl)-3-hydroxypyridine-2-carbonyl]amino}-2,2-dimethylacetic acid ethyl ester;

5-(3-Trifluoromethylphenyl)-N-(1,1-dimethyl-2-amino-2-oxoethyl)-3-hydroxylpyridin-2-yl amide;

5-(3-Trifluoromethylphenyl)-N-(1,1-dimethyl-2-methylamino-2-oxoethyl)-3-hydroxylpyridin-2-yl amide;

5-(3-Trifluoromethylphenyl)-N-(1,1-dimethyl-2-dimethylamino-2-oxoethyl)-3-hydroxylpyridin-2-yl amide;

{[5-(3-Chloro-6-methyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid;

{[5-(3-Chloro-6-methyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid methyl ester;

{[5-(3-Chloro-6-methyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid ethyl ester;

5-(3-Chloro-6-methyl)-N-(2-amino-2-oxoethyl)-3-hydroxylpyridin-2-yl amide;

5-(3-Chloro-6-methyl)-N-(2-methylamino-2-oxoethyl)-3-hydroxylpyridin-2-yl amide;

5-(3-Chloro-6-methyl)-N-(2-dimethylamino-2-oxoethyl)-3-hydroxylpyridin-2-yl amide;

{[5-(3-Chloro-6-methyl)-3-hydroxypyridine-2-carbonyl]amino}-2-methylacetic acid;

{[5-(3-Chloro-6-methyl)-3-hydroxypyridine-2-carbonyl]amino}-2-methylacetic acid methyl ester;

{[5-(3-Chloro-6-methyl)-3-hydroxypyridine-2-carbonyl]amino}-2-methylacetic acid ethyl ester;

5-(3-Chloro-6-methyl)-N-(1-methyl-2-amino-2-oxoethyl)-3-hydroxylpyridin-2-yl amide;

5-(3-Chloro-6-methyl)-N-(1-methyl-2-methylamino-2-oxoethyl)-3-hydroxylpyridin-2-yl amide;

5-(3-Chloro-6-methyl)-N-(1-methyl-2-dimethylamino-2-oxoethyl)-3-hydroxylpyridin-2-yl amide;

{[5-(3-Chloro-6-methyl)-3-hydroxypyridine-2-carbonyl]amino}-2,2-dimethylacetic acid;

{[5-(3-Chloro-6-methyl)-3-hydroxypyridine-2-carbonyl]amino}-2,2-dimethylacetic acid methyl ester;

{[5-(3-Chloro-6-methyl)-3-hydroxypyridine-2-carbonyl]amino}-2,2-dimethylacetic acid ethyl ester;

5-(3-Chloro-6-methyl)-N-(1,1-dimethyl-2-amino-2-oxoethyl)-3-hydroxylpyridin-2-yl amide;

5-(3-Chloro-6-methyl)-N-(1,1-dimethyl-2-methylamino-2-oxoethyl)-3-hydroxylpyridin-2-yl amide; and

5-(3-Chloro-6-methyl)-N-(1,1-dimethyl-2-dimethylamino-2-oxoethyl)-3-hydroxylpyridin-2-yl amide;

{[5-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid;

{[5-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid methyl ester;

{[5-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid ethyl ester;

5-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-N-(2-amino-2-oxoethyl)-3-hydroxylpyridin-2-yl amide;

5-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-N-(2-methylamino-2-oxoethyl)-3-hydroxylpyridin-2-yl amide;

5-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-N-(2-dimethylamino-2-oxoethyl)-3-hydroxylpyridin-2-yl amide;

{[5-(2,3-dihydrobenzo [1,4]dioxin-6-yl)-3-hydroxypyridine-2-carbonyl]amino}-2-methylacetic acid;

{[5-(2,3-dihydrobenzo [1,4]dioxin-6-yl)-3-hydroxypyridine-2-carbonyl]amino}-2-methylacetic acid methyl ester;

{[5-(2,3-dihydrobenzo [1,4]dioxin-6-yl)-3-hydroxypyridine-2-carbonyl]amino}-2-methylacetic acid ethyl ester;

5-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-N-(1-methyl-2-amino-2-oxoethyl)-3-hydroxylpyridin-2-yl amide;

5-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-N-(1-methyl-2-methylamino-2-oxoethyl)-3-hydroxylpyridin-2-yl amide;

5-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-N-(1-methyl-2-dimethylamino-2-oxoethyl)-3-hydroxylpyridin-2-yl amide;

{[5-(2,3-dihydrobenzo [1,4]dioxin-6-yl)-3-hydroxypyridine-2-carbonyl]amino}-2,2-dimethylacetic acid;

{[5-(2,3-dihydrobenzo [1,4]dioxin-6-yl)-3-hydroxypyridine-2-carbonyl]amino}-2,2-dimethylacetic acid methyl ester;

{[5-(2,3-dihydrobenzo [1,4]dioxin-6-yl)-3-hydroxypyridine-2-carbonyl]amino}-2,2-dimethylacetic acid ethyl ester;

5-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-N-(1,1-dimethyl-2-amino-2-oxoethyl)-3-hydroxylpyridin-2-yl amide;

5-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-N-(1,1-dimethyl-2-methylamino-2-oxoethyl)-3-hydroxylpyridin-2-yl amide; and

5-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-N-(1,1-dimethyl-2-dimethylamino-2-oxoethyl)-3-hydroxylpyridin-2-yl amide;

or a pharmaceutically acceptable salt thereof

28. A composition for treating anemia, comprising:

A) One or more compounds having the formula:

wherein R 2 is chosen from:

i) —OR 6 ; or

ii) —NR 7a R 7b ;

R 6 is hydrogen, methyl, or ethyl;

R 7a and R 7b are each independently:

i) hydrogen; or

ii) methyl;

R 3 is hydrogen or methyl;

R 8a and R 8b are each independently hydrogen, methyl, or ethyl;

R 10 represents from 1 to 5 substitutions for hydrogen, said substitutions independently chosen from:

i) fluoro;

ii) chloro;

iii) trifluoromethyl;

iv) methyl; or

v) two adjacent R 10 units can be taken together to form a 6-member ring having one or two oxygen atoms, provided no two oxygen atoms are adjacent to one another in the ring; and

pharmaceutically acceptable salts thereof; and

B) one or more pharmaceutically acceptable excipients.

29. The composition according to claim 28 , wherein the compound is chosen from {[5-(3-Chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, {[5-(4-fluorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, {[5-(3-trifluoromethylphenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, and {[5-(3-chloro-6-methylphenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid.

30. A composition for treating wounds, comprising:

A) One or more compounds having the formula:

wherein R 2 is chosen from:

i) —OR 6 ; or

ii) —NR 7a R 7b ;

R 6 is hydrogen, methyl, or ethyl;

R 7a and R 7b are each independently:

i) hydrogen; or

ii) methyl;

R 3 is hydrogen or methyl;

R 8a and R 8b are each independently hydrogen, methyl, or ethyl;

R 10 represents from 1 to 5 substitutions for hydrogen, said substitutions independently chosen from:

i) fluoro;

ii) chloro;

iii) trifluoromethyl;

iv) methyl; or

v) two adjacent R 10 units can be taken together to form a 6-member ring having one or two oxygen atoms, provided no two oxygen atoms are adjacent to one another in the ring; and

pharmaceutically acceptable salts thereof; and

B) one or more pharmaceutically acceptable excipients.

31. The composition according to claim 30 , wherein the compound is {[5-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid.

32. The compound {[5-(3-Chlorophenyl)-3-hydroxypyridine-2-carbonyl]-amino}acetic acid.

Assignments (9)