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Claims for Patent: 7,473,686

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Claims for Patent: 7,473,686

Title:Thrombopoietin mimetics
Abstract: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.
Inventor(s): Duffy; Kevin J. (Collegeville, PA), Erickson-Miller; Connie (King Of Prussia, PA), Jenkins; Julian (Collegeville, PA), Luengo; Juan I. (Collegeville, PA), Visonneau; Sophie (Collegeville, PA)
Assignee: SmithKline Beecham Corp. (Philadelphia, PA)
Application Number:11/650,651
Patent Claims: 1. The compound: 3'-{N'-[1-(3,4-Dimethylphenyl)-3-methyl-5-oxo-1,5-dihydropyrazol-4-yliden- e]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-yliden- e]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.
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