Pyrimidinones as PI3K inhibitors
The present invention provides pyrimidinones that modulate the activity of phosphoinositide 3-kinases (PI3Ks) and are useful in the treatment of diseases related to the activity of PI3Ks including, for example, inflammatory disorders, immune-based disorders, cancer, and other diseases.
1. A method of inhibiting an activity of PI3Kδ comprising contacting said PI3Kδ with a compound, which is 7-(1-(9H-purin-6-ylamino)ethyl)-6-(3-fluorophenyl)-3-methyl-5H-thiazolo[3,2-a]pyrimidin-5-one, or a pharmaceutically acceptable salt thereof.
2. The method of claim 1 , wherein said compound is a selective inhibitor for PI3Kδ over one or more of PI3Kα, PI3Kβ, and PI3Kγ.
3. A method of treating a disease selected from B cell lymphoma, rheumatoid arthritis, myasthenia gravis, Sjoegren's syndrome, multiple sclerosis, glomerulonephritis, lupus, and inflammation related to rheumatoid arthritis, glomerulonephritis, or lupus, in a patient, comprising administering to said patient a therapeutically effective amount of a compound, which is 7-(1-(9H-purin-6-ylamino)ethyl)-6-(3-fluorophenyl)-3-methyl-5H-thiazolo[3,2-a]pyrimidin-5-one, or a pharmaceutically acceptable salt thereof.
4. The method of claim 1 , wherein the compound is (S)-7-(1-(9H-purin-6-ylamino)ethyl)-6-(3-fluorophenyl)-3-methyl-5H-thiazolo[3,2-a]pyrimidin-5-one, or a pharmaceutically acceptable salt thereof.
5. The method of claim 3 , wherein the disease is B cell lymphoma.
6. The method of claim 5 , wherein the B cell lymphoma is diffuse large B cell lymphoma.
7. The method of claim 3 , wherein the disease is myasthenia gravis.
8. The method of claim 3 , wherein the disease is Sjoegren's syndrome.
9. The method of claim 3 , wherein the disease is multiple sclerosis.
10. The method of claim 3 , wherein the disease is glomerulonephritis.
11. The method of claim 3 , wherein the disease is lupus.
12. The method of claim 3 , wherein the disease is inflammation related to rheumatoid arthritis.
13. The method of claim 3 , wherein the disease is inflammation related to glomerulonephritis.
14. The method of claim 3 , wherein the disease is inflammation related to lupus.
15. The method of claim 3 , wherein the compound is (S)-7-(1-(9H-purin-6-ylamino)ethyl)-6-(3-fluorophenyl)-3-methyl-5H-thiazolo[3,2-a]pyrimidin-5-one, or a pharmaceutically acceptable salt thereof.
16. The method of claim 15 , wherein the disease is B cell lymphoma.
17. The method of claim 16 , wherein the B cell lymphoma is diffuse large B cell lymphoma.
18. The method of claim 15 , wherein the disease is myasthenia gravis.
19. The method of claim 15 , wherein the disease is Sjöegren's syndrome.
20. The method of claim 15 , wherein the disease is multiple sclerosis.
21. The method of claim 13 , wherein the disease is glomerulonephritis.
22. The method of claim 15 , wherein the disease is lupus.
23. The method of claim 15 , wherein the disease is inflammation related to rheumatoid arthritis.
24. The method of claim 15 , wherein the disease is inflammation related to glomerulonephritis.
25. The method of claim 15 , wherein the disease is inflammation related to lupus.