Kinase inhibitor compounds
View Patent ↗The invention relates to kinase inhibitor compounds and methods of identifying and using them. The invention further relates to pharmaceutical compositions and methods for treating disorders, especially cancer.
1. A method of treating cancer in a subject comprising administering to the subject identified as in need thereof a compound selected from the group consisting of:
2-methyl-1-phenyl-4-pyridin-2-yl-2-(2-pyridin-2-ylethyl)butan-1-one;
3-[5-[(4-oxo-4-phenyl-butan-2-ylidene)amino]pentylimino]-1-phenyl-butan-1-one (G13);
2-(diethylaminomethyl)-4-[4-[3-(diethylaminomethyl)-4-hydroxy-phenyl]hex-3-en-3-yl]phenol (G6);
2-dibutoxyphosphoryloxypentanenitrile (G31);
ytterbium(+3) cation trihydroxide (G33);
4-[(1S)-6,7-diethoxy-1,2,3,4-tetrahydroisoquinolin-1-yl]benzonitrile (G40);
G6 lead compound
or a salt, hydrate or solvate thereof ;
wherein said cancer is selected from the group consisting of leukemias, lymphomas, myelomas, myeloproliferative disorders, pancreatic cancer, and glioma.
2. The method of claim 1 , wherein the leukemia is selected from the group consisting of: chronic myelogenous leukemia (CML), acute myeloid leukemia (AML) and acute promyelocytic leukemia (APL).
3. A method of inhibiting JAK2 in a subject identified as in need of such treatment, comprising administering a compound selected from the group consisting of:
2-methyl-1-phenyl-4-pyridin-2-yl-2-(2-pyridin-2-ylethyl)butan-1-one;
3-[5-[(4-oxo-4-phenyl-butan-2-ylidene)amino]pentylimino]-1-phenyl-butan-1-one (G13);
2-(diethylaminomethyl)-4-[4-[3-(diethylaminomethyl)-4-hydroxy-phenyl]hex-3-en-3-yl]phenol (G6);
2-dibutoxyphosphoryloxypentanenitrile (G31);
ytterbium(+3) cation trihydroxide (G33);
4-[(1S)-6,7-diethoxy-1,2,3,4-tetrahydroisoquinolin-1-yl]benzonitrile (G40);
G6 lead compound
or a salt, hydrate or solvate thereof.
4. The method of claim 1 , wherein the compound is 2-(diethylaminomethyl)-4-[4-[3-(diethylaminomethyl)-4-hydroxy-phenyl]hex-3-en-3-yl]phenol (G6).
5. The method of claim 1 , wherein the compound is selected from the group consisting of
or a salt, hydrate or solvate thereof.
6. The method of claim 5 , wherein the compound is selected from the group consisting of: D4, D5, D28 and D30.
7. The method of claim 1 , wherein the compound or a salt, hydrate or solvate thereof, is an inhibitor of the JAK2-V617F mutant.
8. The method of claim 1 , wherein the compound or a salt, hydrate or solvate thereof, inhibits JAK2 autophosphorylation.
9. A kit comprising a compound selected from the group consisting of:
2-methyl-1-phenyl-4-pyridin-2-yl-2-(2-pyridin-2-ylethyl)butan-1-one;
3-[5-[(4-oxo-4-phenyl-butan-2-ylidene)amino]pentylimino]-1-phenyl-butan-1-one (G13);
2-(diethylaminomethyl)-4-[4-[3-(diethylaminomethyl)-4-hydroxy-phenyl]hex-3-en-3-yl]phenol (G6);
2-dibutoxyphosphoryloxypentanenitrile (G31);
ytterbium(+3) cation trihydroxide (G33);
4-[(1S)-6,7-diethoxy-1,2,3,4-tetrahydroisoquinolin-1-yl]benzonitrile (G40);
G6 lead compound
and instructions for use in treating leukemias, lymphomas, myelomas, myeloproliferative disorders, pancreatic cancer, or glioma.
10. The method of claim 1 , wherein the compound is administered intravenously.
11. The method of claim 10 , wherein the compound is 2-(diethylaminomethyl)-4-[4-[3-(diethylaminomethyl)-4-hydroxy-phenyl]hex-3-en-3-yl]phenol (G6).