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Generated: August 18, 2017

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Title:3'-[(2Z)-[1-(3,4-dimethylphenyl)-1,5-dihydro-3-methyl-5-oxo-4H-pyrazol-4-y- lidene]hydrazino]-2'-hydroxy-[1,1'-biphenyl]-3-carboxylic acid bis-(monoethanolamine)
Abstract: An improved thrombopoietin mimetic, the bis-(monoethanolamine) salt of 3'-[(2Z)-[1-(3,4-dimethylphenyl)-1,5-dihydro-3-methyl-5-oxo-4H-pyrazol-4-- ylidene]hydrazino]-2'-hydroxy-[1,1'-biphenyl]-3-carboxylic acid.
Inventor(s): Moore; Stephen (Lingfield, GB)
Assignee: GlaxoSmithKline LLC (Wilmington, DE)
Filing Date:Oct 10, 2013
Application Number:14/050,976
Claims:1. An in vitro or ex vivo method for enhancing stimulation of megakaryocyte maturation and/or platelet production which comprises adding an effective amount of the compound 3'-[(2Z)-[1-(3,4-dimethylphenyl)-1,5-dihydro-3-methyl-5-oxo-4H-pyrazol-4-- ylidene]hydrazino]-2'-hydroxy-[1,1'-biphenyl]-3-carboxylic acid bis-(monoethanolamine) to a culture medium of stem cells, bone marrow cells, cord-blood cells or peripheral blood cells.

2. A method of claim 1, wherein the megakaryocytes or platelets are returned to the mammal following chemotherapy or radiation therapy.

3. An in vitro or ex vivo method for enhancing the survival and/or proliferation of stem cells, bone marrow cells, cord-blood cells, peripheral blood cells or other types of cells expressing the TPO receptor in culture which comprises culturing said cell in a medium containing an effective amount of the compound 3'-[(2Z)-[1-(3,4-dimethylphenyl)-1,5-dihydro-3-methyl-5-oxo-4H-pyrazol-4-- ylidene]hydrazino]-2'-hydroxy-[1,1'-biphenyl]-3-carboxylic acid bis-(monoethanolamine).

4. A method of claim 3 further comprising co-administration of a therapeutically effective amount of a colony stimulating factor, cytokine, chemokine, interleukin or cytokine receptor agonist.

5. A method of claim 3 wherein the stem cells are returned to the subject following chemotherapy or radiation therapy.

6. A method of treating of neutropenia in a mammal, including a human, in need thereof which comprises administering to such mammal a therapeutically effective amount of the compound 3'-[(2Z)-[1-(3,4-dimethylphenyl)-1,5-dihydro-3-methyl-5-oxo-4H-pyrazol-4-- ylidene]hydrazino]-2'-hydroxy-[1,1'-biphenyl]-3-carboxylic acid bis-(monoethanolamine).

7. An in vitro or ex vivo method for enhancing stimulation of neutrophil production which comprises adding an effective amount of the compound 3'-[(2Z)-[1-(3,4-dimethylphenyl)-1,5-dihydro-3-methyl-5-oxo-4H-pyrazol-4-- ylidene]hydrazino]-2'-hydroxy-[1,1'-biphenyl]-3-carboxylic acid bis-(monoethanolamine) to a culture medium of stem cells, bone marrow cells, cord-blood cells, peripheral blood cells or other types of cells expressing the TPO receptor.

8. A method of claim 7, wherein the neutrophils are returned to the subject following chemotherapy or radiation therapy.
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