SALTS OF (S)-7-(1-(9H-PURIN-6-YLAMINO)ETHYL)-6-(3-FLUOROPHENYL)-3-METHYL-5H-THIAZOLO[3,2-A]PYRIMIDIN-5-ONE
The present invention relates to salt forms of the phosphoinositide 3-kinase (PI3K) inhibitor (S)-7-(1-(9H-purin-6-ylamino)ethyl)-6-(3-fluorophenyl)-3-methyl-5H-thiazolo[3,2-a]pyrimidin-5-one, pharmaceutical compositions comprising the same, and methods of using the salts and compositions for the treatment of PI3K-associated diseases such as cancer.
1 . A pharmaceutically acceptable salt form of a compound of Formula I:
wherein the salt is an adipic acid salt, a hydrochloric acid salt, a methanesulfonic acid salt, a gentisic acid salt, or an ethanesulfonic acid salt.
2 . The salt form of claim 1 which is an adipic acid salt.
3 . The salt form of claim 1 which is a hydrochloric acid salt.
4 . The salt form of claim 1 which is a methanesulfonic acid salt.
5 . The salt form of claim 1 which is a gentisic acid salt.
6 . The salt form of claim 1 which is an ethanesulfonic acid salt. The salt form of claim 1 which is crystalline.
8 . The salt form of claim 1 which is anhydrous.
9 . The salt form of claim 1 which is substantially isolated.
10 . A composition comprising the salt form of claim 1 and a pharmaceutically acceptable carrier.
11 . A method of treating a disease in a patient, wherein the disease is associated with abnormal expression or activity of a PI3K kinase, comprising administering to said patient a therapeutically effective amount of a salt form of claim 1 .
12 . The method of claim 11 , wherein the disease is osteoarthritis, restenosis, atherosclerosis, bone disorders, arthritis, diabetic retinopathy, psoriasis, benign prostatic hypertrophy, inflammation, angiogenesis, pancreatitis, kidney disease, inflammatory bowel disease, myasthenia gravis, multiple sclerosis, or Sjögren's syndrome.
13 . The method claim 11 , wherein more than one of the salts is administered.
14 . The method of claim 11 , wherein the salt is administered in combination with a kinase inhibitor that inhibits a kinase other than a PI3K kinase.
15 . A method of treating an immune-based disease in a patient, comprising administering to the patient a therapeutically effective amount of a salt form of claim 1 .
16 . The method of claim 15 , wherein said immune-based disease is rheumatoid arthritis, allergy, asthma, glomerulonephritis, lupus, or inflammation related to any of the aforementioned.
17 . A method of treating a cancer in a patient, comprising administering to the patient a therapeutically effective amount of a salt form of claim 1 .
18 . The method of claim 17 , wherein the cancer is breast, prostate, colon, endometrial, brain, bladder, skin, uterus, ovary, lung, pancreatic, renal, gastric, or a hematological cancer.
19 . The method of claim 18 , wherein the hematological cancer is acute myeloblastic leukemia, chronic myeloid leukemia, B cell lymphoma, chronic lymphocytic leukemia (CLL), Non-Hodgkins lymphoma, hairy cell leukemia, Mantle cell lymphoma, Burkitt lymphoma, small lymphocytic lymphoma, follicular lymphoma, lymphoplasmacytic lymphoma, extranodal marginal zone lymphoma, activated B-cell like (ABC) diffuse large B cell lymphoma, or germinal center B cell (GCB) diffuse large B cell lymphoma.
20 . A method of treating a lung disease in a patient, comprising administering to said patient a therapeutically effective amount of a salt form of claim 1 .
21 . The method of claim 20 , wherein said lung disease is acute lung injury (ALI) or adult respiratory distress syndrome (ARDS).
22 . A method of preparing a salt form of claim 1 comprising combining the compound of Formula I with adipic acid, hydrochloric acid, methanesulfonic acid, gentisic acid, or ethanesulfonic acid.