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. (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.
2. A pharmaceutical composition comprising a compound of claim 1 and at least one pharmaceutically acceptable carrier.
3. The pharmaceutical composition of claim 2 , wherein the compound has an enantiomeric excess of at least 98%.
4. A method treating indolent non-Hodgkin's lymphoma 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.
5. The method of claim 4 , wherein 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 is administered.
6. The method of claim 5 , wherein the (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 has an enantiomeric excess of at least 95%.
7. The method of claim 5 , wherein the (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 has an enantiomeric excess of at least 98%.
8. The method of claim 4 , further comprising the step of administering simultaneously or sequentially to the subject at least one other anti-cancer agent.
9. A method of treating follicular lymphoma 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.
10. The method of claim 9 , wherein 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 is administered.
11. The method of claim 10 , wherein the (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 has an enantiomeric excess of at least 95%.
12. The method of claim 10 , wherein the (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 has an enantiomeric excess of at least 98%.
13. The method of claim 9 , further comprising the step of administering simultaneously or sequentially to the subject at least one other anti-cancer agent.