Thrombopoietin mimetics
View Patent ↗Invented are non-peptide TPO mimetics. Also invented are novel processes and intermediates used in the preparation of the presently invented compounds. Also invented is a method of treating thrombocytopenia, in a mammal, including a human, in need thereof which comprises administering to such mammal an effective amount of a selected hydroxy-1-azobenzene derivative.
1. The compound:
3′-{N′-[1-(3,4-Dimethylphenyl)-3-methyl-5-oxo-1,5-dihydropyrazol-4-ylidene]hydrazino}-2′-hydroxybiphenyl-3-carboxylic acid, or a pharmaceutically acceptable salt thereof.
2. The compound 3′-{N′-[1-(3,4-Dimethylphenyl)-3-methyl-5-oxo-1,5-dihydropyrazol-4-ylidene]hydrazino}-2′-hydroxybiphenyl-3-carboxylic acid, or an ester thereof.
3. A compound of claim 2 , wherein the compound is in the form of an ester.
4. A pharmaceutical composition which comprises a compound of claim 1 and a pharmaceutically acceptable carrier.
5. A pharmaceutical composition which comprises a compound of claim 2 and a pharmaceutically acceptable carrier.
6. A method of therapeutic therapy of thrombocytopenia in a human in need thereof which comprises administering to such human a therapeutically effective amount of a compound of claim 1 .
7. The method of claim 6 wherein the compound is administered orally.
8. The method of claim 6 wherein the compound is administered parenterally.
9. The method of claim 6 further comprising co-administering a therapeutically effective amount of an agent selected from the group consisting of: a colony stimulating factor, cytokine, chemokine, and an interleukin or cytokine receptor agonist or antagonist.
10. The method of claim 9 wherein the agent is selected from the group consisting of: G-CSF, GM-CSF, TPO, M-CSF, EPO, Gro-beta, IL-11, SCF, FLT3 ligand, LIF, IL-3, IL-6, IL-1, NESP, SD-01, IL-8, and IL-5.
11. The method of claim 10 wherein the agent is selected from the group consisting of: G-CSF, GM-CSF, TPO, M-CSF, EPO, and IL-11.
12. The method of claim 6 wherein said thrombocytopenia is due to myelosuppression caused by chemotherapy or radiation therapy.
13. The method of claim 6 wherein said thrombocytopenia is due to an organ transplant.
14. The method of claim 6 wherein said thrombocytopenia is due to bone marrow, stem cell, or liver transplant.
15. The method of claim 6 wherein said thrombocytopenia is due to idiopathic thrombocytopenia purpura (ITP).
16. The method of claim 6 wherein said thrombocytopenia is due to myelodysplastic syndromes (MDS), aplastic anemia or leukemia.
17. The method of claim 6 wherein said thrombocytopenia is due to viral, fungal, microbial or parasitic infection.
18. The method of claim 6 wherein said thrombocytopenia is due to liver dysfunction.
19. The method of claim 6 wherein said thrombocytopenia is due to surgical procedures.
20. The method of claim 6 wherein said thrombocytopenia is due to treatment with antiviral or antibiotic agents.
21. A process for preparing a pharmaceutical composition containing a pharmaceutically acceptable carrier or diluent and an effective amount of a compound of claim 1 , which process comprises bringing said compound into association with the pharmaceutically acceptable carrier or diluent.
22. A process for preparing a pharmaceutical composition containing a pharmaceutically acceptable carrier or diluent and an effective amount of a compound of claim 2 , which process comprises bringing said compound into association with the pharmaceutically acceptable carrier or diluent.
23. The method of claim 6 wherein said thrombocytopenia is due to exposure to radiation.
24. The method of claim 6 wherein said thrombocytopenia is due to treatment with antiviral agents.
25. The method of claim 6 wherein said thrombocytopenia is due to treatment with antibiotic agents.