Certain chemical entities, compositions and methods
Chemical entities that modulate PI3 kinase activity, pharmaceutical compositions containing the chemical entities, and methods of using these chemical entities for treating diseases and conditions associated with P13 kinase activity are described herein.
1. A method of treating cancer in a subject, comprising administering to the subject an effective amount of a compound of formula:
or a pharmaceutically acceptable salt thereof, wherein the cancer is leukemia or lymphoma.
2. The method of claim 1 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
3. The method of claim 1 , wherein the cancer is leukemia.
4. The method of claim 3 , wherein the leukemia is B-cell acute lymphoblastic leukemia (B-ALL), acute lymphocytic leukemia, hairy cell leukemia, myelodysplasia, myeloproliferative disorders, acute myelogenous leukemia (AML), chronic lymphocytic leukemia (CLL), multiple myeloma (MM), or myelodysplastic syndrome (MDS).
5. The method of claim 1 , wherein the cancer is chronic lymphocytic leukemia.
6. The method of claim 1 , wherein the cancer is non-Hodgkin lymphomas.
7. The method of claim 1 , wherein the cancer is acute lymphocytic leukemia (ALL).
8. The method of claim 1 , wherein the cancer is diffuse large B-cell lymphoma.
9. The method of claim 1 , wherein the cancer is myelodysplastic syndrome (MDS).
10. The method of claim 1 , wherein the cancer is adult T-cell lymphoma.
11. The method of claim 1 , wherein the cancer is acute myelogenous leukemia (AML).
12. The method of claim 1 , wherein the cancer is chronic myelogenous leukemia (CML).
13. The method of claim 1 , wherein the cancer is myeloproliferative disorders.
14. The method of claim 1 , wherein the cancer is mast cell leukemia.
15. The method of claim 1 , wherein the cancer is Hodgkin disease.
16. The method of claim 1 , wherein the cancer is B-cell acute lymphoblastic leukemia.
17. The method of claim 1 , wherein the cancer is T-cell acute lymphoblastic leukemia.
18. The method of claim 1 , wherein the cancer is multiple myeloma (MM).
19. The method of claim 1 , further comprising administering one or more second therapeutic agents selected from chemotherapeutic agents, cytotoxic agents, and radiation.
20. The method of claim 19 , wherein the second therapeutic agent is an anti-CD20 antibody.
21. The method of claim 19 , wherein the second therapeutic agent is rituximab.
22. The method of claim 19 , wherein the second therapeutic agent is chlorambucil.
23. The method of claim 19 , wherein the second therapeutic agent is chlorambucil, chlornaphazine, estramustine, ifosfamide, mechlorethamine, mechlorethamine oxide hydrochloride, melphalan, novembichin, phenesterine, prednimustine, trofosfamide, uracil mustard, fludarabine, or cyclophosphamide.
24. The method of claim 1 , wherein the cancer is lymphoma.
25. The method of claim 24 , wherein the lymphoma is Hodgkin disease or non-Hodgkin lymphoma.
26. The method of claim 24 , wherein the lymphoma is diffuse large B-cell lymphoma, small non-cleaved cell lymphoma, or adult T-cell lymphoma.
27. The method of claim 24 , wherein the lymphoma is B-cell immunoblastic lymphoma.
28. The method of claim 19 , wherein the second therapeutic agent is fludarabine, cyclophosphamide, or rituximab, or a combination thereof.