Details for Patent: 7,335,649

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 Corporation (Philadelphia, PA)
Filing Date:	Nov 09, 2006
Application Number:	11/558,071
Claims:	1. A compound selected from the group consisting essentially of: 3-{N'-[1-(3,4-dimethylphenyl)-3-methyl-5-oxo-1,5-dihydropyrazol-4-ylidene- ]hydrazino}-2-hydroxy-3'-(tetrazol-5-yl)biphenyl, and a pharmaceutically acceptable salt, a hydrate, a solvate, and an ester, thereof. 2. A pharmaceutical composition which comprises a compound of claim 1 and a pharmaceutically acceptable carrier. 3. A method of treating thrombocytopenia in a human in need thereof which comprises administering to such human a therapeutically effective amount of the compound of claim 1. 4. The method of claim 3 wherein the compound is administered orally. 5. The method of claim 3 wherein the compound is administered parenterally. 6. The method of claim 3 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. 7. The method of claim 6 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. 8. The method of claim 3 wherein said thrombocytopenia is due to myelosuppression caused by chemotherapy or radiation therapy. 9. The method of claim 3 wherein said thrombocytopenia is due to an organ transplant. 10. The method of claim 3 wherein said thrombocytopenia is due to bone marrow, stem cell, or liver transplant. 11. The method of claim 3 wherein said thrombocytopenia is due to idiopathic thrombocytopenia purpura (ITP). 12. The method of claim 3 wherein said thrombocytopenia is due to myelodysplastic syndromes (MDS), aplastic anemia or leukemia. 13. The method of claim 3 wherein said thrombocytopenia is due to viral, fungal, microbial or parasitic infection. 14. The method of claim 3 wherein said thrombocytopenia is due to liver dysfunction. 15. The method of claim 3 wherein said thrombocytopenia is due to surgical procedures. 16. The method of claim 3 wherein said thrombocytopenia is due to treatment with antiviral or antibiotic agents. 17. A process for preparing a pharmaceutical composition containing a pharmaceutically acceptable carrier or diluent and an effective amount of the compound of claim 1, which process comprises bringing said compound into association with the pharmaceutically acceptable carrier or diluent. 18. A compound selected from the group consisting essentially of: 3'-{N'-[1-(4-tert-butylphenyl)-3-methyl-5-oxo-1,5-dihydropyrazol-4-yliden- e]hydrazino}-2'-hydroxybiphenyl-3-carboxylic acid, and a pharmaceutically acceptable salt, a hydrate, a solvate, and an ester, thereof. 19. A compound selected from the group consisting essentially of: 3-Aza-3'-{N'-[1-(4-tert-butylpbenyl)-3-methyl-5-oxo-1,5-dihydropyrazol-4-- ylidene]hydrazino}-2'-hydroxybiphenyl-5-carboxylic acid, and a pharmaceutically acceptable salt, a hydrate, a solvate, and an ester, thereof. 20. The compound 3-{N'-[1-(3,4-dimethylphenyl)-3-methyl-5-oxo-1,5-dihydropyrazol-4-ylidene- ]hydrazino}-2-hydroxy-3'-(tetrazol-5-yl)biphenyl, or a pharmaceutically acceptable salt thereof. 21. A compound of claim 20, wherein the compound is in the form of a pharmaceutically acceptable salt. 22. A compound of claim 20, wherein the compound is 3-{N'-[1-(3,4-dimethylphenyl)-3-methyl-5-oxo-1,5-dihydropyrazol-4-ylidene- ]hydrazino}-2-hydroxy-3'-(tetrazol-5-yl)biphenyl. 23. The compound 3-{N'-[1-(3,4-dimethylphenyl)-3-methyl-5-oxo-1,5-dihydropyrazol-4-ylidene- ]hydrazino}-2-hydroxy-3'-(tetrazol-5-yl)biphenyl, or an ester thereof. 24. A compound of claim 23, wherein the compound is in the form of an ester. 25. A pharmaceutical composition which comprises a compound of claim 20 and a pharmaceutically acceptable carrier. 26. A pharmaceutical composition which comprises a compound of claim 21 and a pharmaceutically acceptable carrier. 27. A pharmaceutical composition which comprises the compound of claim 22 and a pharmaceutically acceptable carrier. 28. A pharmaceutical composition which comprises a compound of claim 23 and a pharmaceutically acceptable carrier. 29. A pharmaceutical composition which comprises a compound of claim 24 and a pharmaceutically acceptable carrier. 30. A process for preparing a pharmaceutical composition containing a pharmaceutically acceptable carrier or diluent and an effective amount of a compound of claim 20, which process comprises bringing said compound into association with the pharmaceutically acceptable carrier or diluent. 31. A process for preparing a pharmaceutical composition containing a pharmaceutically acceptable carrier or diluent and an effective amount of a compound of claim 23, which process comprises bringing said compound into association with the pharmaceutically acceptable carrier or diluent. 32. A method of claim 6 wherein the co-administered agent is selected from the group consisting of: a colony stimulation factor, cytokine and chemokine. 33. A method of claim 7 wherein the agent is selected from the group consisting of G-CSF, GM-CSF, EPO and IL-5.