Prolyl Hydroxylase Inhibitors

Abstract

The invention described herein relates to certain bicyclic heteroaromatic N-substituted glycine derivatives of formula (I)

Description

Claims

1. A compound of formula (I):

2. A compound according to claim 1 wherein: R1 is hydrogen, —C1C10alkyl, —C1-C10alkyl-NR3R4, —C3-C8cycloalkyl, —C1-C10alkyl, —C3-C8cycloalkyl, —C3-C8-heterocycloalkyl, —C1-C10alkyl-C3-C8-heterocycloalkyl, —C1-C10alkyl-aryl, —C1-C10alkyl-aryl-C1-C4alkyl, or —C1-C10alkyl-aryl-halo;R2 is —NR6R7 or —OR8;R3 and R4 are each independently hydrogen or —C1-C10 alkyl;R6 and R7 are each independently selected from the group consisting of hydrogen, —C1-C10 alkyl, —C2-C10 alkenyl, —C2-C10 alkynyl, —C3-C8 cycloalkyl, —C3-C8 heterocycloalkyl, aryl and heteroaryl;R8 is H, a cation, or C1-C10alkyl;each R9 is independently selected from the group consisting of hydrogen, halogen, trifluoromethyl, —OR5, —N(R3)CH2C(O)OR5, unsubstituted or substituted-phenyl or —C1-C4 alkylphenyl, and —C1-C4 alkyl;each R5 is hydrogen or —C1-C4alkyl;or a pharmaceutically acceptable salt thereof

3. A compound according to claim 1 or 2 wherein; R1 is hydrogen, —C1-C6alkyl, —C1-C4alkyl-NR3R4, —C1-C4alkyl-C3-C6cycloalkyl, —C1-C4alkyl-phenyl, —C1-C4alkyl-phenyl-halo;R2 is —OR8;R3 and R4 are each independently hydrogen or —C1-C4alkyl;each R5 is independently hydrogen or C1-C4alkyl;R8 is H, a cation, or C1-C10alkyl;each R9 is independently selected from the group consisting of hydrogen, halogen, trifluoromethyl, —N(R3)CH2C(O)OR5, —OR5, unsubstituted or substituted phenyl or —C1-C4 alkylphenyl, and —C1-C4 alkyl;or a pharmaceutically acceptable salt thereof.

4. A compound according to claim 2 wherein W is nitrogen and X, Y and Z are CR9, or a pharmaceutically acceptable salt thereof.

5. A compound according to claim 3 wherein W is nitrogen and X, Y and Z are CR9, or a pharmaceutically acceptable salt thereof.

6. A compound according to claim 2 wherein X is nitrogen and W, Y and Z are CR9, or a pharmaceutically acceptable salt thereof.

7. A compound according to claim 3 wherein X is nitrogen and W, Y and Z are CR9, or a pharmaceutically acceptable salt thereof.

8. A compound according to claim 2 wherein W and Z are nitrogen and X and Y are CR9 or a pharmaceutically acceptable salt thereof.

9. A compound according to claim 3 wherein W and Z are nitrogen and X and Y are CR9 or a pharmaceutically acceptable salt thereof.

10. A compound according to claim 2 wherein Y is nitrogen and W, X and Z are CR9, or a pharmaceutically acceptable salt thereof.

11. A compound according to claim 3 wherein Y is nitrogen and W, X and Z are CR9, or a pharmaceutically acceptable salt thereof.

12. A compound according to claim 2 wherein W and Y are nitrogen and X and Z are CR9, or a pharmaceutically acceptable salt thereof.

13. A compound according to claim 3 wherein W and Y are nitrogen and X and Z are CR9, or a pharmaceutically acceptable salt thereof.

14. A compound according to claim 2 wherein Z is nitrogen and W, X and Y are CR9, or a pharmaceutically acceptable salt thereof.

15. A compound according to claim 3 wherein Z is nitrogen and W, X and Y are CR9, or a pharmaceutically acceptable salt thereof.

16. A compound according to claim 1 which is: N-{[1-(2-cyclopropylethyl)-4-hydroxy-2-oxo-1,2-dihydro-1,8-naphthyridin-3-yl]carbonyl}glycine;N-{[4-hydroxy-1-(3-methylbutyl)-2-oxo-1,2-dihydro-1,8-naphthyridin-3-yl]carbonyl}glycine;N-{[1-(3,3-dimethylbutyl)-4-hydroxy-2-oxo-1,2-dihydro-1,8-naphthyridin-3-yl]carbonyl}glycine;N-{[4-hydroxy-2-oxo-1-(phenylmethyl)-1,2-dihydro-1,8-naphthyridin-3-yl]carbonyl}glycine;N-({1-[2-(dimethylamino)ethyl]-4-hydroxy-2-oxo-1,2-dihydro-1,8-naphthyridin-3-yl}carbonyl)glycine;N-{[4-hydroxy-2-oxo-1-(phenylmethyl)-1,2-dihydro-1,7-naphthyridin-3-yl]carbonyl}glycine;N-[(4-hydroxy-2-oxo-1,2-dihydro-1,7-naphthyridin-3-yl)carbonyl]glycine;N-[(8-hydroxy-6-oxo-4,6-dihydropyrido [2,3-b]pyrazin-7-yl)carbonyl]glycine;N-{[1-(3,3-dimethylbutyl)-4-hydroxy-7-methyl-2-oxo-1,2-dihydro-1,8-naphthyridin-yl]carbonyl}glycine;N-{[6-chloro-1-(3,3-dimethylbutyl)-4-hydroxy-2-oxo-1,2-dihydro-1,8-naphthyridin-3-yl]carbonyl}glycine;N-{[1-(3,3-dimethylbutyl)-4-hydroxy-2-oxo-7-(trifluoromethyl)-1,2-dihydro-1,8-naphthyridin-3-yl]carbonyl}glycineN-{[1-(3,3-dimethylbutyl)-6-fluoro-4-hydroxy-2-oxo-1,2-dihydro-1,8-naphthyridin-3-yl]carbonyl}glycine;N-{[6-bromo-1-(3,3-dimethylbutyl)-4-hydroxy-2-oxo-1,2-dihydro-1,8-naphthyridin-3-yl]carbonyl}glycine;N-[(1-{[4-(1,1-dimethylethyl)phenyl]methyl}-6-fluoro-4-hydroxy-2-oxo-1,2-dihydro-1,8-naphthyridin-3-yl)carbonyl]glycine;{[6-{[(carboxymethyl)amino]carbonyl}-8-(3,3-dimethylbutyl)-5-hydroxy-2-methyl-7-oxo-7,8-dihydro-1,8-naphthyridin-4-yl]amino }acetic acid;N-{[5-hydroxy-7-oxo-2-phenyl-8-(phenylmethyl)-7,8-dihydropyrido [2,3-d]pyrimidin-6-yl]carbonyl}glycine;N-[(1-{[4-(1,1-dimethylethyl)phenyl]methyl}-4-hydroxy-2-oxo-1,2-dihydro-1,8-naphthyridin-3-yl)carbonyl]glycine;N-{[1-{[4-(1,1-dimethylethyl)phenyl]methyl}-4-hydroxy-2-oxo-7-(trifluoromethyl)-1,2-dihydro-1,8-naphthyridin-3-yl]carbonyl}glycine;N-({1-[(2-chlorophenyl)methyl]-4-hydroxy-2-oxo-1,2-dihydro-1,8-naphthyridin-3-yl}carbonyl)glycine;N-{[1-(3,3-dimethylbutyl)-4-hydroxy-7-methyl-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl]carbonyl}glycine;N-{[8-hydroxy-6-oxo-5-(phenylmethyl)-5,6-dihydropyrido[2,3-b]pyrazin-7-yl]carbonyl}glycine;N-{[4-hydroxy-6-(methyloxy)-2-oxo-1-(phenylmethyl)-1,2-dihydro-1,5-naphthyridin-3-yl]carbonyl}glycine;N-({5-[(2-chlorophenyl)methyl]-8-hydroxy-6-oxo-5,6-dihydropyrido[2,3-b]pyrazin-7-yl}carbonyl)glycine;N-{[4-hydroxy-2,6-dioxo-1-(phenylmethyl)-1,2,5,6-tetrahydro-1,5-naphthyridin-3-yl]carbonyl}glycine;or a pharmaceutically acceptable salt thereof.

17. A method for treating anemia in a mammal, which method comprises administering an effective amount of a compound of formula (I) according to claim 1 or a salt thereof to a mammalian suffering from anemia.

18. A pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof according to claim 1 and one or more of pharmaceutically acceptable carriers, diluents or excipients.