Heterocyclic compounds and thrombopoietin receptor activators
A compound represented by the formula (1): wherein A is a nitrogen atom or CR 4 , B is an oxygen atom, a sulfur atom or NR 9 (provided that when A is a nitrogen atom, B is not NH), R 1 is a C 2-14 aryl group, L 1 is a bond, CR 10 R 11 , an oxygen atom, a sulfur atom or NR 12 , X is OR 13 , SR 13 or NR 14 NR 15 , R 2 is a hydrogen atom, a formyl group, a C 1-10 alkyl group or the like, L 2 is a bond or the like, L 3 is a bond, CR 17 R 18 , an oxygen atom, a sulfur atom or NR 19 , L 4 is a bond, CR 20 R 21 , an oxygen atom, a sulfur atom or NR 22 , Y is an oxygen atom, a sulfur atom or NR 23 , and R 3 is a C 2-14 aryl group, a tautomer, prodrug or pharmaceutically acceptable salt of the compound or a solvate thereof.
1. A compound represented by the formula (1)
wherein
A is a CH, and
B is sulfur;
R 1 is a phenyl, wherein the phenyl is substituted with one or more substituents selected from the group consisting of chlorine, trifluoromethyl, and t-butyl,
L 1 is a bond,
X is OH,
R 2 is methyl,
L 2 is a bond,
L 3 is NH,
L 4 is NH,
Y is sulfur, and
R 3 is phenyl substituted with a carboxy group,
a tautomer, prodrug or pharmaceutically acceptable salt of the compound.
2. 4-{[(2-[1-[5-(4-t-butylphenyl)-4-hydroxy-3-thienyl]ethylidene]hydrazine)cabonothioyl]amino}benzoic acid, a tautomer thereof or a pharmaceutically acceptable salt thereof.
3. 4-([(2-(1-[5-(3,4-dichlorophenyl)-4-hydroxy-3-thienyl]ethyliden)hydrazine)carbonothioyl]amino)benzoic acid, a tautomer thereof or a pharmaceutically acceptable salt thereof.
4. 4-[(2-{1-[5-(4-trifluoromethylphenyl)-4-hydroxy-3-thienyl]ethylidene}hydrazino)carbonyl]benzoic acid, a tautomer thereof or a pharmaceutically acceptable salt thereof.
5. 4-{[(2-{1-[5-(3-trifluoromethylphenyl)-4-hydroxy-3-thienyl]ethylidene}hydrazino)-carbonothioyl]amino}benzoic acid, a tautomer thereof or a pharmaceutically acceptable salt thereof.
6. 3-{[(2-(1-[5-(3,4-dichlorophenyl)-4-hydroxy-3-thienyl]ethylidene)hydrazine)-carbonothioyl]amino}benzoic acid, a tautomer thereof or a pharmaceutically acceptable salt thereof.
7. 3-([(2-(1-[5-(4-t-butylphenyl)-4-hydroxy-3-thienyl]ethylidene)hydrazine)-carbonothioyl]amino)benzoic acid, a tautomer thereof or a pharmaceutically acceptable salt thereof.
8. 3-([(2-(1-[5-(4-chlorophenyl)-4-hydroxy-3-thienyl]ethylidene)hydrazine)-carbonothioyl]amino)benzoic acid, a tautomer thereof or a pharmaceutically acceptable salt thereof.
9. 3-([(2-(1-[5-(3-chlorophenyl)-4-hydroxy-3-thienyl]ethylidene)hydrazine)-carbonothioyl]amino)benzoic acid, a tautomer thereof or a pharmaceutically acceptable salt thereof.
10. A composition comprising at least one compound of claim 1 , a tautomer thereof, a prodrug thereof, or a pharmaceutically acceptable salt thereof; and at least one carrier.
11. A composition comprising the compound of claim 2 , a tautomer thereof, or a pharmaceutically acceptable salt thereof; and at least one carrier.
12. A composition comprising the compound of claim 3 , a tautomer thereof, or a pharmaceutically acceptable salt thereof; and at least one carrier.
13. A composition comprising the compound of claim 4 , a tautomer thereof, or a pharmaceutically acceptable salt thereof; and at least one carrier.
14. A composition comprising the compound of claim 5 , a tautomer thereof, or a pharmaceutically acceptable salt thereof; and at least one carrier.
15. A composition comprising the compound of claim 6 , a tautomer thereof, or a pharmaceutically acceptable salt thereof; and at least one carrier.
16. A composition comprising the compound of claim 7 , a tautomer thereof, or a pharmaceutically acceptable salt thereof; and at least one carrier.
17. A composition comprising the compound of claim 8 , a tautomer thereof, or a pharmaceutically acceptable salt thereof; and at least one carrier.
18. A composition comprising the compound of claim 9 , a tautomer thereof or a pharmaceutically acceptable salt thereof; and at least one carrier.
19. A method of treating thrombocytopenia in a patient in need thereof, the method comprising administering to the patient an effective amount of at least one compound of claim 1 , a tautomer thereof, a prodrug thereof, or a pharmaceutically acceptable salt thereof to treat the thrombocytopenia.
20. A method of treating thrombocytopenia in a patient in need thereof, the method comprising administering to the patient an effective amount of at least one compound of claim 2 , a tautomer thereof, or a pharmaceutically acceptable salt thereof to treat the thrombocytopenia.
21. A method of treating thrombocytopenia in a patient in need thereof, the method comprising administering to the patient an effective amount of at least one compound of claim 3 , a tautomer thereof, or a pharmaceutically acceptable salt thereof to treat the thrombocytopenia.
22. A method of treating thrombocytopenia in a patient in need thereof, the method comprising administering to the patient an effective amount of at least one compound of claim 4 , a tautomer thereof, or a pharmaceutically acceptable salt thereof to treat the thrombocytopenia.
23. A method of treating thrombocytopenia in a patient in need thereof, the method comprising administering to the patient an effective amount of at least one compound of claim 5 , a tautomer thereof, or a pharmaceutically acceptable salt thereof to treat the thrombocytopenia.
24. A method of treating thrombocytopenia in a patient in need thereof, the method comprising administering to the patient an effective amount of at least one compound of claim 6 , a tautomer thereof, or a pharmaceutically acceptable salt thereof to treat the thrombocytopenia.
25. A method of treating thrombocytopenia in a patient in need thereof, the method comprising administering to the patient an effective amount of at least one compound of claim 7 , a tautomer thereof, or a pharmaceutically acceptable salt thereof to treat the thrombocytopenia.
26. A method of treating thrombocytopenia in a patient in need thereof, the method comprising administering to the patient an effective amount of at least one compound of claim 8 , a tautomer thereof, or a pharmaceutically acceptable salt thereof to treat the thrombocytopenia.
27. A method of treating thrombocytopenia in a patient in need thereof, the method comprising administering to the patient an effective amount of at least one compound of claim 9 , a tautomer thereof, or a pharmaceutically acceptable salt thereof to treat the thrombocytopenia.
28. A method of increasing platelets, vascular endothelial cells and/or endothelial progenitor cells, the method comprising administering to the patient an effective amount of at least one compound of claim 1 , a tautomer thereof, a prodrug thereof, or a pharmaceutically acceptable salt thereof to increase platelets, vascular endothelial cells and/or endothelial progenitor cells.
29. A method of increasing platelets, vascular endothelial cells and/or endothelial progenitor cells, the method comprising administering to the patient an effective amount of at least one compound of claim 2 , a tautomer thereof or a pharmaceutically acceptable salt thereof to increase platelets, vascular endothelial cells and/or endothelial progenitor cells.
30. A method of increasing platelets, vascular endothelial cells and/or endothelial progenitor cells, the method comprising administering to the patient an effective amount of at least one compound of claim 3 , a tautomer thereof or a pharmaceutically acceptable salt thereof to increase platelets, vascular endothelial cells and/or endothelial progenitor cells.
31. A method of increasing platelets, vascular endothelial cells and/or endothelial progenitor cells, the method comprising administering to the patient an effective amount of at least one compound of claim 4 , a tautomer thereof or a pharmaceutically acceptable salt thereof to increase platelets, vascular endothelial cells and/or endothelial progenitor cells.
32. A method of increasing platelets, vascular endothelial cells and/or endothelial progenitor cells, the method comprising administering to the patient an effective amount of at least one compound of claim 5 , a tautomer thereof or a pharmaceutically acceptable salt thereof to increase platelets, vascular endothelial cells and/or endothelial progenitor cells.
33. A method of increasing platelets, vascular endothelial cells and/or endothelial progenitor cells, the method comprising administering to the patient an effective amount of at least one compound of claim 6 , a tautomer thereof or a pharmaceutically acceptable salt thereof to increase platelets, vascular endothelial cells and/or endothelial progenitor cells.
34. A method of increasing platelets, vascular endothelial cells and/or endothelial progenitor cells, the method comprising administering to the patient an effective amount of at least one compound of claim 7 , a tautomer thereof or a pharmaceutically acceptable salt thereof to increase platelets, vascular endothelial cells and/or endothelial progenitor cells.
35. A method of increasing platelets, vascular endothelial cells and/or endothelial progenitor cells, the method comprising administering to the patient an effective amount of at least one compound of claim 8 , a tautomer thereof or a pharmaceutically acceptable salt thereof to increase platelets, vascular endothelial cells and/or endothelial progenitor cells.
36. A method of increasing platelets, vascular endothelial cells and/or endothelial progenitor cells, the method comprising administering to the patient an effective amount of at least one compound of claim 9 , a tautomer thereof or a pharmaceutically acceptable salt thereof to increase platelets, vascular endothelial cells and/or endothelial progenitor cells.