Salts and forms of a WEE1 inhibitor
The salt, such as adipate salt Form A, and freebase forms of Compound A are WEE1 inhibitors. Such salts and/or forms and freebase forms, as well as pharmaceutically acceptable salts and compositions thereof, are useful for treating diseases or conditions, including conditions characterized by excessive cellular proliferation, such as breast cancer.
1 . (R)-2-allyl-1-(7-ethyl-7-hydroxy-6,7-dihydro-5H-cyclopenta[b]pyridin-2-yl)-6-((4-(4-methylpiperazin-1-yl)phenyl)amino)-1,2-dihydro-3H-pyrazolo [3,4-d]pyrimidin-3-one (Compound A):
wherein Compound A is selected from the group consisting of adipate salt Form A of Compound A, freebase Form E of Compound A, freebase Form F of Compound A and freebase Form J of Compound A, wherein:
the adipate salt form A is characterized by one or more peaks in an X-ray powder diffraction pattern, wherein the one or more peaks are selected from 15.40 degrees 2θ ±0.2 degrees 2θ, 16.58 degrees 2θ ±0.2 degrees 2θ, 22.12 degrees 2θ ±0.2 degrees 2θ and 22.88 degrees 2θ ±0.2 degrees 2θ; and
the freebase Form E of Compound A is a hydrate and is characterized by one or more peaks in an X-ray powder diffraction pattern, wherein the one or more peaks are selected from 6.20 degrees 2θ ±0.2 degrees 2θ, 12.40 degrees 2θ ±0.2 degrees 2θ, 18.96 degrees 2θ ±0.2 degrees 2θ and 22.62 degrees 2θ ±0.2 degrees 2θ;
the freebase Form F of Compound A is characterized by one or more peaks in an X-ray powder diffraction pattern, wherein the one or more peaks are selected from 5.14 degrees 2θ ±0.2 degrees 2θ, 6.24 degrees 2θ ±0.2 degrees 2θ, 10.19 degrees 2θ ±0.2 degrees 2θ and 12.40 degrees 2θ ±0.2 degrees 2θ; and
the freebase Form J is an anhydrate and is characterized by one or more peaks in an X-ray powder diffraction pattern, wherein the one or more peaks are selected from 6.08 degrees 2θ ±0.2 degrees 2θ, 10.58 degrees 2θ ±0.2 degrees 2θ, 19.42 degrees 2θ ±0.2 degrees 2θ, 21.93 degrees 2θ ±0.2 degrees 2θ and 23.23 degrees 2θ ±0.2 degrees 2θ.
2 . The compound of claim 1 , wherein the Compound A is adipate salt Form A of Compound A.
3 . The compound of claim 2 , wherein the adipate salt Form A is characterized by peaks in an X-ray powder diffraction pattern, wherein the peaks are −15.40 degrees 2θ ±0.2 degrees 2θ, 16.58 degrees 2θ ±0.2 degrees 2θ, 22.12 degrees 2θ ±0.2 degrees 2θ and 22.88 degrees 2θ ±0.2 degrees 2θ.
4 . The compound of claim 2 , wherein the adipate salt Form A is characterized by a differential scanning calorimetry (DSC) thermogram comprising an endotherm in the range of about 75° C. to about 183° C.
5 . The compound of claim 1 , wherein the Compound A is freebase Form E of Compound A as a hydrate.
6 . The compound of claim 5 , wherein the freebase Form E is characterized by peaks in an X-ray powder diffraction pattern, wherein the peaks are 6.20 degrees 2θ ±0.2 degrees 2θ, 12.40 degrees 2θ ±0.2 degrees 2θ, 18.96 degrees 2θ ±0.2 degrees 2θ and 22.62 degrees 2θ ±0.2 degrees 2θ.
7 . The compound of claim 5 , wherein the freebase Form E is characterized by a DSC thermogram comprising an endotherm in the range of about 105° C. to about 125° C.
8 . The compound of claim 5 , wherein the freebase Form E is characterized by a DSC thermogram comprising an endotherm at approximately 115° C.
9 . The compound of claim 5 , wherein the freebase Form E is characterized by a weight loss of about 3.8% when heated from about 28 to ° C. about 150° C.
10 . The compound of claim 1 , wherein the Compound A is freebase Form F of Compound A.
11 . The compound of claim 10 , wherein the freebase Form F is characterized by peaks in an X-ray powder diffraction pattern, wherein the peaks are 5.14 degrees 2θ ±0.2 degrees 2θ, 6.24 degrees 2θ ±0.2 degrees 2θ, 10.19 degrees 2θ ±0.2 degrees 2θ and 12.40 degrees 2θ ±0.2 degrees 2θ.
12 . The compound of claim 10 , wherein the freebase Form F is characterized by a DSC thermogram comprising an endotherm in the range of about 163° C. to about 171° C.
13 . The compound of claim 1 , wherein the Compound A is Form J of Compound A as an anhydrate.
14 . The compound of claim 13 , wherein the freebase Form J is characterized by peaks in an X-ray powder diffraction pattern, wherein peaks are 6.08 degrees 2θ ±0.2 degrees 2θ, 10.58 degrees 2θ ±0.2 degrees 2θ, 19.42 degrees 2θ ±0.2 degrees 2θ, 21.93 degrees 2θ ±0.2 degrees 2θ and 23.23 degrees 2θ ±0.2 degrees 2θ.
15 . A pharmaceutical composition comprising an effective amount of Compound A of claim 1 , and a pharmaceutically acceptable carrier, diluent, excipient or combination thereof.
16 . A method for ameliorating or treating a malignant growth or tumor comprising administering an effective amount of Compound A of claim 1 , or a pharmaceutically acceptable salt thereof, to a subject in need thereof, wherein the malignant growth or tumor is due to a cancer selected from a breast cancer, a cervical cancer, an ovarian cancer, an uterine cancer, a vaginal cancer, a vulvar cancer, a brain cancer, a cervicocerebral cancer, an esophageal cancer, a thyroid cancer, a lung cancer, a stomach cancer, a gallbladder cancer, a bile duct cancer, a liver cancer, a pancreatic cancer, a colon cancer, a rectal cancer, a choriocarcinoma, an uterus body cancer, an uterocervical cancer, a renal pelvis cancer, a ureter cancer, a bladder cancer, a prostate cancer, a penis cancer, a testicular cancer, a fetal cancer, a Wilms' cancer, a skin cancer, a malignant melanoma, a neuroblastoma, an osteosarcoma, an Ewing's tumor, a soft part sarcoma, an acute leukemia, a chronic lymphatic leukemia, a chronic myelocytic leukemia, polycythemia vera, a malignant lymphoma, multiple myeloma, a Hodgkin's lymphoma and a non-Hodgkin's lymphoma.
17 . The method of claim 16 , wherein the cancer is a breast cancer, a cervical cancer, an ovarian cancer, an uterine cancer, a vaginal cancer or a vulvar cancer.
18 . The method of claim 16 , wherein the cancer is an ovarian cancer.
19 . The method of claim 16 , wherein the cancer is a lung cancer.
20 . The method of claim 19 , wherein the lung cancer is a small cell lung cancer.
21 . The method of claim 16 , wherein the cancer is an uterine cancer.
22 . The method of claim 16 , wherein the cancer is an osteosarcoma.
23 . A method for ameliorating or treating a malignant growth or tumor comprising contacting the malignant growth or tumor with an effective amount of Compound A of claim 1 , or a pharmaceutically acceptable salt thereof, to a subject in need thereof, wherein the malignant growth or tumor is due to a cancer selected from a breast cancer, a cervical cancer, an ovarian cancer, an uterine cancer, a vaginal cancer, a vulvar cancer, a brain cancer, a cervicocerebral cancer, an esophageal cancer, a thyroid cancer, a lung cancer, a stomach cancer, a gallbladder cancer, a bile duct cancer, a liver cancer, a pancreatic cancer, a colon cancer, a rectal cancer, a choriocarcinoma, an uterus body cancer, an uterocervical cancer, a renal pelvis cancer, a ureter cancer, a bladder cancer, a prostate cancer, a penis cancer, a testicular cancer, a fetal cancer, a Wilms' cancer, a skin cancer, a malignant melanoma, a neuroblastoma, an osteosarcoma, an Ewing's tumor, a soft part sarcoma, an acute leukemia, a chronic lymphatic leukemia, a chronic myelocytic leukemia, polycythemia vera, a malignant lymphoma, multiple myeloma, a Hodgkin's lymphoma and a non-Hodgkin's lymphoma.