Dual selective PI3 delta and gamma kinase inhibitors
The present invention relates to dual delta (δ) and gamma (γ) PI3K protein kinase modulators, methods of preparing them, pharmaceutical compositions containing them and methods of treatment, prevention and/or amelioration of Pi3K kinase mediated diseases or disorders with them.
1. A composition comprising (S)-2-(1-(9H-purin-6-ylamino)propyl)-3-(3-fluorophenyl)-4H-chromen-4-one or a pharmaceutically acceptable salt thereof, wherein the composition is substantially free of (R)-2-(1-(9H-purin-6-ylamino)propyl)-3-(3-fluorophenyl)-4H-chromen-4-one and pharmaceutically acceptable salts thereof.
2. A composition comprising (S)-2-(1-(9H-purin-6-ylamino)propyl)-3-(3-fluorophenyl)-4H-chromen-4-one, wherein the composition is substantially free of (R)-2-(1-(9H-purin-6-ylamino)prop yl)-3-(3-fluorophenyl)-4H-chromen-4-one.
3. A composition comprising (S)-2-(1-(9H-purin-6-ylamino)propyl)-3-(3-fluorophenyl)-4H-chromen-4-one or a pharmaceutically acceptable salt thereof, wherein the composition has an enantiomeric excess greater than about 90% relative to (R)-2-(1-(9H-purin-6-ylamino)propyI)-3-(3-fluorophenyl)-4H-chromen-4-one.
4. A composition comprising (S)-2-(1-(9H-purin-6-ylamino)propyl)-3-(3-fluorophenyl)-4H-chromen-4-one, wherein the composition has an enantiomeric excess greater than about 90% relative to (R)-2-(1-(9H-purin-6-ylamino)propyI)-3-(3-fluorophenyl)-4H-chromen-4-one %.
5. A pharmaceutical composition comprising (S)-2-(1-(9H-purin-6-ylamino)propyl)-3-(3-fluorophenyl)-4H-chromen-4-one or a pharmaceutically acceptable salt thereof and at least one pharmaceutically acceptable carrier, wherein the composition is substantially free of (R)-2-(1-(9H-purin-6-ylamino)propyl)-3-(3-fluorophenyl)-4H-chromen-4-one and pharmaceutically acceptable salts thereof.
6. A pharmaceutical composition comprising (S)-2-(1-(9H-purin-6-ylamino)propyl)-3-(3-fluorophenyl)-4H-chromen-4-one and at least one pharmaceutically acceptable carrier, wherein the composition is substantially free of (R)-2-(1-(9H-purin-6-ylamino)propyl)-3-(3-fluorophenyl)-4H-chromen-4-one.
7. A pharmaceutical composition comprising (S)-2-(1-(9H-purin-6-ylamino)propyl)-3-(3-fluorophenyl)-4H-chromen-4-one or a pharmaceutically acceptable salt thereof and at least one pharmaceutically acceptable carrier, wherein the composition has an enantiomeric excess greater than about 90% relative to (R)-2-(1-(9H-purin-6-ylamino)propyI)-3-(3-fluorophenyl)-4H-chromen-4-one.
8. A pharmaceutical composition comprising (S)-2-(1-(9H-purin-6-ylamino)propyl)-3-(3-fluorophenyl)-4H-chromen-4-one and at least one pharmaceutically acceptable carrier, wherein the composition has an enantiomeric excess greater than about 90% relative to (R)-2-(1-(9H-purin-6-ylamino)propyI)-3-(3-fluorophenyl)-4H-chromen-4-one.
9. The composition of claim 3 , wherein the composition has an enantiomeric excess of (S)-2-(1-(9H-purin-6-ylamino)propyl)-3-(3-fluorophenyl)-4H-chromen-4-one or a pharmaceutically acceptable salt thereof greater than about 95%.
10. The composition of claim 3 , wherein the composition has an enantiomeric excess of (S)-2-(1-(9H-purin-6-ylamino)propyl)-3-(3-fluorophenyl)-4H-chromen-4-one or a pharmaceutically acceptable salt thereof greater than about 98%.
11. The composition of claim 3 , wherein the composition has an enantiomeric excess of (S)-2-(1-(9H-purin-6-ylamino)propyl)-3-(3-fluorophenyl)-4H-chromen-4-one or a pharmaceutically acceptable salt thereof greater than about 99%.
12. The composition of claim 4 , wherein the composition has an enantiomeric excess of (S)-2-(1-(9H-purin-6-ylamino)propyl)-3-(3-fluorophenyl)-4H-chromen-4-one greater than about 95%.
13. The composition of claim 4 , wherein the composition has an enantiomeric excess of (S)-2-(1-(9H-purin-6-ylamino)propyl)-3-(3-fluorophenyl)-4H-chromen-4-one greater than about 98%.
14. The composition of claim 4 , wherein the composition has an enantiomeric excess of (S)-2-(1-(9H-purin-6-ylamino)propyl)-3-(3-fluorophenyl)-4H-chromen-4-one greater than about 99%.
15. The pharmaceutical composition of claim 7 , wherein the composition has an enantiomeric excess of (S)-2-(1-(9H-purin-6-ylamino)propyl)-3-(3-fluorophenyl)-4H-chromen-4-one or a pharmaceutically acceptable salt thereof greater than about 95%.
16. The pharmaceutical composition of claim 7 , wherein the composition has an enantiomeric excess of (S)-2-(1-(9H-purin-6-ylamino)propyl)-3-(3-fluorophenyl)-4H-chromen-4-one or a pharmaceutically acceptable salt thereof greater than about 98%.
17. The pharmaceutical composition of claim 7 , wherein the composition has an enantiomeric excess of (S)-2-(1-(9H-purin-6-ylamino)propyl)-3-(3-fluorophenyl)-4H-chromen-4-one or a pharmaceutically acceptable salt thereof greater than about 99%.
18. The pharmaceutical composition of claim 8 , wherein the composition has an enantiomeric excess of (S)-2-(1-(9H-purin-6-ylamino)propyl)-3-(3-fluorophenyl)-4H-chromen-4-one greater than about 95%.
19. The pharmaceutical composition of claim 8 , wherein the composition has an enantiomeric excess of (S)-2-(1-(9H-purin-6-ylamino)propyl)-3-(3-fluorophenyl)-4H-chromen-4-one greater than about 98%.
20. The pharmaceutical composition of claim 8 , wherein the composition has an enantiomeric excess of (S)-2-(1-(9H-purin-6-ylamino)propyl)-3-(3-fluorophenyl)-4H-chromen-4-one greater than about 99%.
21. A method of inhibiting a catalytic activity of a PI3 δ kinase present in a cell, comprising contacting the cell with an effective amount of a composition of claim 1 .
22. A method of inhibiting a catalytic activity of a PI3 γ kinase present in a cell, comprising contacting the cell with an effective amount of a composition of claim 1 .
23. A method of inhibiting a catalytic activity of a PI3 δ kinase and PI3 γ kinase present in a cell, comprising contacting the cell with an effective amount of a composition of claim 1 .
24. The method of claim 21 , wherein the inhibition takes place in a cell, wherein the cell is in a subject suffering from leukemia.
25. A method of ameliorating leukemia, the method comprising administering an effective amount of a composition of claim 1 to a patient in need thereof.
26. The method of claim 25 , wherein the leukemia is acute lymphocytic leukemia, acute lymphoblastic leukemia, chronic lymphocytic leukemia (CLL), or acute myeloid leukemia (AML).
27. A method of inhibiting a catalytic activity of a PI3 δ kinase present in a cell, comprising contacting the cell with an effective amount of a pharmaceutical composition of claim 5 .
28. A method of inhibiting a catalytic activity of a PI3 γ kinase present in a cell, comprising contacting the cell with an effective amount of a pharmaceutical composition of claim 5 .
29. A method of inhibiting a catalytic activity of a PI3 δ kinase and PI3 γ kinase present in a cell, comprising contacting the cell with an effective amount of a pharmaceutical composition of claim 5 .
30. The method of claim 27 , wherein the inhibition takes place in a cell, wherein the cell is in a subject suffering from leukemia.
31. A method of ameliorating leukemia, the method comprising administering an effective amount of a pharmaceutical composition of claim 5 to a patient in need thereof.
32. The method of claim 31 , wherein the leukemia is acute lymphocytic leukemia, acute lymphoblastic leukemia, chronic lymphocytic leukemia (CLL), or acute myeloid leukemia (AML).