Non-peptide thrombopoietin receptor agonist in the treatment of cancer and pre-cancerous syndromes
View Patent ↗Invented is a method of treating cancer or a pre-cancerous syndrome in a mammal, including a human, in need thereof which comprises the administration of an effective amount of a non-peptide thrombopoietin (TPO) receptor agonist to such mammal, suitably a human.
1. A method of treating acute myelogenous leukemia (AML) in a mammal in need thereof which comprises the administration of a therapeutically effective amount of a compound selected from:
3′-{N′-[1-(3,4-Dimethylphenyl)-3-methyl-5-oxo-1,5-dihydropyrazol-4-ylidene]hydrazino}-2′-hydroxybiphenyl-3-carboxylic acid;
3-{N′-[1-(3,4-dimethylphenyl)-3-methyl-5-oxo-1,5-dihydropyrazol-4-ylidene]hydrazino}-2-hydroxy-3′-tetrazol-5-ylbiphenyl; and
1-(3-chloro-5-{[4-(4-chlorothiophen-2-yl)-5-(4-cyclohexylpiperazin-1-yl)thiazol-2-yl]carbamoyl}pyridine-2-yl)piperidine-4-carboxylic acid;
or a pharmaceutically acceptable salt thereof wherein said mammal is not suffering from thrombocytopenia.
2. The method according to claim 1 wherein the mammal is a human.
3. The method according to claim 2 wherein the compound is administered orally.
4. The method according to claim 2 wherein the compound is administered parenterally.
5. The method according to claim 3 wherein the compound is:
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.
6. The method according to claim 5 wherein the compound is:
3′-{N′-[1-(3,4-Dimethylphenyl)-3-methyl-5-oxo-1,5-dihydropyrazol-4-ylidene]hydrazino}-2′-hydroxybiphenyl-3-carboxylic acid bis-(monoethanolamine).
7. The method according to claim 3 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-ylbiphenyl;
or a pharmaceutically acceptable salt thereof.
8. The method according to claim 3 wherein the compound is:
1-(3-chloro-5-{[4-(4-chlorothiophen-2-yl)-5-(4-cyclohexylpiperazin-1-yl)thiazol-2-yl]carbamoyl}pyridine-2-yl)piperidine-4-carboxylic acid;
or a pharmaceutically acceptable salt thereof.