Selective PI3K delta inhibitors
The present invention relates to selective inhibitors of PI3K delta protein kinases, methods of preparing them, pharmaceutical compositions containing them and methods of treatment and/or prevention of kinase mediated diseases or disorders with them.
1. A method of treating chronic lymphocytic leukemia (CLL) in a human subject in need thereof comprising administering to the human subject an effective amount of (S)-2-(1-(4-amino-3-(3-fluoro-4-isopropoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-6-fluoro-3-(3-fluorophenyl)-4H-chromen-4-one or a pharmaceutically acceptable salt thereof.
2. The method of claim 1 , wherein (S)-2-(1-(4-amino-3-(3-fluoro-4-isopropoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-6-fluoro-3-(3-fluorophenyl)-4H-chromen-4-one or a pharmaceutically acceptable salt thereof has an enantiomeric excess of at least 95%.
3. The method of claim 1 , further comprising the step of administering simultaneously or sequentially to the human subject in need thereof at least one other anti-cancer agent.
4. A method of treating chronic lymphocytic leukemia (CLL) in a human subject in need thereof comprising administering to the human subject an effective amount of (S)-2-(1-(4-amino-3-(3-fluoro-4-isopropoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-6-fluoro-3-(3-fluorophenyl)-4H-chromen-4-one 4-methylbenzenesulfonate.
5. The method of claim 4 , further comprising the step of administering simultaneously or sequentially to the human subject in need thereof at least one other anti-cancer agent.
6. A method of treating diffuse large B-cell lymphoma (DLBCL) in a human subject in need thereof comprising administering to the human subject an effective amount of (S)-2-(1-(4-amino-3-(3-fluoro-4-isopropoxyphenyl)-1H-pyrazolo [3,4-d]pyrimidin-1-yl)ethyl)-6-fluoro-3-(3-fluorophenyl)-4H-chromen-4-one or a pharmaceutically acceptable salt thereof.
7. The method of claim 6 , wherein (S)-2-(1-(4-amino-3-(3-fluoro-4-isopropoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-6-fluoro-3-(3-fluorophenyl)-4H-chromen-4-one or a pharmaceutically acceptable salt thereof has an enantiomeric excess of at least 95%.
8. The method of claim 6 , further comprising the step of administering simultaneously or sequentially to the human subject in need thereof at least one other anti-cancer agent.
9. A method of treating diffuse large B-cell lymphoma (DLBCL) in a human subject in need thereof comprising administering to the human subject an effective amount of (S)-2-(1-(4-amino-3-(3-fluoro-4-isopropoxyphenyl)-1H-pyrazolo [3,4-d]pyrimidin-1-yl)ethyl)-6-fluoro-3-(3-fluorophenyl)-4H-chromen-4-one 4-methylbenzenesulfonate.
10. The method of claim 9 , further comprising the step of administering simultaneously or sequentially to the human subject in need thereof at least one other anti-cancer agent.
11. A method of treating non-Hodgkin lymphoma (NHL) in a human subject in need thereof comprising administering to the human subject an effective amount of (S)-2-(1-(4-amino-3-(3-fluoro-4-isopropoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-6-fluoro-3-(3-fluorophenyl)-4H-chromen-4-one or a pharmaceutically acceptable salt thereof.
12. The method of claim 11 , wherein (S)-2-(1-(4-amino-3-(3-fluoro-4-isopropoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1- yl)ethyl)-6-fluoro-3-(3-fluorophenyl)-4H-chromen-4-one or a pharmaceutically acceptable salt thereof has an enantiomeric excess of at least 95%.
13. The method of claim 11 , further comprising the step of administering simultaneously or sequentially to the human subject in need thereof at least one other anti-cancer agent.
14. A method of treating non-Hodgkin lymphoma (NHL) in a human subject in need thereof comprising administering to the human subject an effective amount of (S)-2-(1-(4-amino-3-(3-fluoro-4-isopropoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-6-fluoro-3-(3-fluorophenyl)-4H-chromen-4-one 4-methylbenzenesulfonate.
15. The method of claim 14 , further comprising the step of administering simultaneously or sequentially to the human subject in need thereof at least one other anti-cancer agent.