Triazolopyridine compound, and action thereof as prolyl hydroxylase inhibitor or erythropoietin production-inducing agent
View Patent ↗The present invention provides a triazolopyridine compound having a prolyl hydroxylase inhibitory action and an erythropoietin production-inducing ability. The present invention relates to a compound represented by the following formula [I]: wherein each symbol is as defined in the specification, or a pharmaceutically acceptable salt thereof, or a solvate thereof, as well as a prolyl hydroxylase inhibitor or erythropoietin production-inducing agent containing the compound. The compound of the present invention shows a prolyl hydroxylase inhibitory action and an erythropoietin production-inducing ability and is useful as a prophylactic or therapeutic agent for various diseases and pathologies (disorders) caused by decreased production of erythropoietin.
1. A compound represented by the following formula [I], or a pharmaceutically acceptable salt thereof, or a solvate thereof:
wherein
the partial structural formula:
is a group represented by:
R 1 is
(1) a hydrogen atom,
(2) a C 1-6 alkyl group,
(3) a C 6-14 aryl group,
(4) a C 3-8 cycloalkyl group,
(5) a C 6-14 aryl-C 1-6 alkyl group, or
(6) a C 3-8 cycloalkyl-C 1-6 alkyl group;
R 2 is
(2) a C 1-10 alkyl group,
(3) a C 6-14 aryl group optionally substituted by the same or different 1 to 5 substituents selected from the following group B,
(4) a C 3-8 cycloalkyl group optionally substituted by the same or different 1 to 5 substituents selected from the following group B,
(5) a C 3-8 cycloalkenyl group optionally substituted by the same or different 1 to 5 substituents selected from the following group B,
(6) a heteroaryl group optionally substituted by the same or different 1 to 5 substituents selected from the following group B (wherein the heteroaryl has, besides carbon atom, 1 to 6 hetero atoms selected from nitrogen atom, oxygen atom and sulfur atom),
(7) a C 6-14 aryl-C 1-6 alkyl group (wherein C 6-14 aryl is optionally substituted by the same or different 1 to 5 substituents selected from the following group B), or
(8) a C 3-8 cycloalkyl-C 1-6 alkyl group (wherein C 3-8 cycloalkyl is optionally substituted by the same or different 1 to 5 substituents selected from the following group B);
R 3 is
(1) a hydrogen atom,
(2) a halogen atom,
(3) a C 1-6 alkyl group,
(4) a C 6-14 aryl group,
(5) a C 3-8 cycloalkyl group, or
(6) a C 6-14 aryl-C 1-6 alkyl group; and
R 4 and R 5 are each independently
(1) a hydrogen atom, or
(2) a C 1-6 alkyl group,
group B:
(a) a halogen atom,
(b) a C 1-6 alkyl group,
(c) a C 3-8 cycloalkyl group,
(d) a cyano group, and
(e) a halo-C 1-6 alkyl group.
2. The compound according to claim 1 , wherein both R 4 and R 5 are hydrogen atoms, or a pharmaceutically acceptable salt thereof, or a solvate thereof.
3. The compound according to claim 1 , wherein R 3 is a hydrogen atom, or a pharmaceutically acceptable salt thereof, or a solvate thereof.
4. The compound according to claim 1 , wherein R 1 is a hydrogen atom, or a pharmaceutically acceptable salt thereof, or a solvate thereof.
5. The compound according to claim 1 , wherein R 2 is
(1) a C 1-10 alkyl group,
(2) a C 6-14 aryl group optionally substituted by the same or different 1 to 5 substituents selected from the above-mentioned group B,
(3) a C 6-14 aryl-C 1-6 alkyl group (wherein C 6-14 aryl is optionally substituted by the same or different 1 to 5 substituents selected from the above-mentioned group 13), or
(4) a C 3-8 cycloalkyl-C 1-6 alkyl group (wherein C 3-8 cycloalkyl is optionally substituted by the same or different 1 to 5 substituents selected from the above-mentioned group B), or a pharmaceutically acceptable salt thereof, or a solvate thereof.
6. The compound according to claim 2 , wherein R 3 is a hydrogen atom, or a pharmaceutically acceptable salt thereof, or a solvate thereof.
7. The compound according to claim 6 , wherein R 1 is a hydrogen atom, or a pharmaceutically acceptable salt thereof, or a solvate thereof.
8. The compound according to claim 7 , wherein R 2 is
(1) a C 1-10 alkyl group, or
(2) a C 6-14 aryl-C 1-6 alkyl group (wherein C 6-14 aryl is optionally substituted by the same or different 1 to 5 substituents selected from the above-mentioned group B),
or a pharmaceutically acceptable salt thereof, or a solvate thereof.
9. A compound represented by the following formula [I-1] or a pharmaceutically acceptable salt thereof, or a solvate thereof:
wherein the partial structural formula:
is a group represented by:
R 11 is
(1) a hydrogen atom,
(2) a C 1-6 alkyl group,
(3) a phenyl group,
(4) a C 3-8 cycloalkyl group,
(5) a phenyl-C 1-6 alkyl group, or
(6) a C 3-8 cycloalkyl-C 1-6 alkyl group;
R 21 is
(2) a C 1-10 alkyl group,
(3) a phenyl group optionally substituted by the same or different 1 to 5 substituents selected from the following group B,
(4) a C 3-8 cycloalkyl group,
(5) a C 3-8 cycloalkenyl group,
(6) a thienyl group optionally substituted by the same or different 1 to 5 substituents selected from the following group B,
(7) a phenyl-C 1-6 alkyl group (wherein phenyl is optionally substituted by the same or different 1 to 5 substituents selected from the following group B), or
(8) a C 3-8 cycloalkyl-C 1-6 alkyl group;
R 31 is
(1) a hydrogen atom,
(2) a halogen atom,
(3) a C 1-6 alkyl group,
(4) a phenyl group,
(5) a C 3-8 cycloalkyl group, or
(6) a phenyl-C 1-6 alkyl group; and
R 41 and R 51 are each independently
(1) a hydrogen atom, or
(2) a C 1-6 alkyl group
group B:
(a) a halogen atom,
(b) a C 1-6 alkyl group,
(c) a C 3-8 cycloalkyl group,
(d) a cyano group, and
(e) a halo-C 1-6 alkyl group.
10. A compound represented by the following formula:
or a pharmaceutically acceptable salt thereof, or a solvate thereof.
11. A compound represented by the following formula:
or a pharmaceutically acceptable salt thereof, or a solvate thereof.
12. A compound represented by the following formula:
or a pharmaceutically acceptable salt thereof, or a solvate thereof.
13. A compound represented by the following formula:
or a pharmaceutically acceptable salt thereof, or a solvate thereof.
14. A compound represented by the following formula:
or a pharmaceutically acceptable salt thereof, or a solvate thereof.
15. A compound represented by the following formula:
or a pharmaceutically acceptable salt thereof, or a solvate thereof.
16. A compound represented by the following formula:
or a pharmaceutically acceptable salt thereof, or a solvate thereof.
17. A compound represented by the following formula:
or a pharmaceutically acceptable salt thereof, or a solvate thereof.
18. A compound represented by the following formula:
or a pharmaceutically acceptable salt thereof, or a solvate thereof.
19. A compound represented by the following formula:
or a pharmaceutically acceptable salt thereof, or a solvate thereof.
20. A compound represented by the following formula:
or a pharmaceutically acceptable salt thereof, or a solvate thereof.
21. A pharmaceutical composition comprising the compound according to claim 1 , or a pharmaceutically acceptable salt thereof, or a solvate thereof, and a pharmaceutically acceptable carrier.
22. A method of inhibiting prolyl hydroxylase, comprising administering an effective amount of the compound according to claim 1 , or a pharmaceutically acceptable salt thereof, or a solvate thereof to a mammal.
23. A method of inducing erythropoietin production, comprising administering an effective amount of the compound according to claim 1 , or a pharmaceutically acceptable salt thereof, or a solvate thereof to a mammal.
24. A method of treating anemia, comprising administering an effective amount of the compound according to claim 1 , or a pharmaceutically acceptable salt thereof, or a solvate thereof to a mammal.
25. A method of treating renal anemia, comprising administering an effective amount of the compound according to claim 1 , or a pharmaceutically acceptable salt thereof, or a solvate thereof to a mammal.
26. A pharmaceutical composition comprising the compound according to any one of claims 10 to 20 , or a pharmaceutically acceptable salt thereof, or a solvate thereof, and a pharmaceutically acceptable carrier.
27. A method of inhibiting prolyl hydroxylase, comprising administering an effective amount of the compound according to any one of claims 10 to 20 , or a pharmaceutically acceptable salt thereof, or a solvate thereof to a mammal.
28. A method of inducing erythropoietin production, comprising administering an effective amount of the compound according to any one of claims 10 to 20 , or a pharmaceutically acceptable salt thereof, or a solvate thereof to a mammal.
29. A method of treating anemia, comprising administering an effective amount of the compound according to any one of claims 10 to 20 , or a pharmaceutically acceptable salt thereof, or a solvate thereof to a mammal.
30. A method of treating renal anemia, comprising administering an effective amount of the compound according to any one of claims 10 to 20 , or a pharmaceutically acceptable salt thereof, or a solvate thereof to a mammal.