CDK9 inhibitors and polymorphs thereof for use as agents for treatment of cancer
A crystalline form and/or polymorph of a compound having the following structure (I), including tautomeric and zwitterionic forms thereof, are provided: Methods associated with preparation and use of the polymorphs, and pharmaceutical compositions comprising the same are also provided. Also provided are methods for preparing a compound having formula (I), or a salt, tautomer or zwitterionic form thereof.
1. A method for treating a cancer in a mammal in need thereof, comprising administering to the mammal crystalline Form B of a compound having the following structure (I):
or a zwitterionic form thereof, in an amount of from about 1 mg to about 50 mg per day, wherein crystalline Form B is characterized by an x-ray powder diffraction pattern comprising at least three peaks at 2-theta angles selected from the group consisting of 4.8±0.2°, 10.8±0.2°, 13.7±0.2°, 14.9±0.2°, 20.0±0.2° and 24.6±0.2°.
2. The method of claim 1 , wherein crystalline Form B is characterized by an x-ray powder diffraction pattern comprising peaks at the following 2-theta angles: 10.8±0.2°, 14.9±0.2° and 20.0±0.2°.
3. The method of claim 1 , wherein crystalline Form B has an x-ray powder diffraction pattern substantially in accordance with that depicted in FIG. 1 .
4. The method of claim 1 , wherein crystalline Form B is a compound having structure (II):
5. The method of claim 1 , wherein about 32 mg per day of crystalline Form B of a compound having structure (I), or a zwitterionic form thereof, is administered to the mammal.
6. The method of claim 1 , wherein crystalline Form B of a compound having structure (I), or a zwitterionic form thereof, is administered to the mammal once per day.
7. The method of claim 1 , wherein crystalline Form B of a compound having structure (I), or a zwitterionic form thereof, is administered to the mammal twice per day.
8. The method of claim 1 , wherein crystalline Form B of a compound having structure (I), or a zwitterionic form thereof, is administered to the mammal daily.
9. The method of claim 1 , wherein the cancer comprises a solid tumor.
10. The method of claim 1 , wherein the cancer is prostate cancer.
11. The method of claim 1 , wherein the cancer is a sarcoma.
12. The method of claim 11 , wherein the sarcoma is Kaposi sarcoma, Ewing sarcoma, osteosarcoma, rhabdomyosarcoma, soft tissue sarcoma or uterine sarcoma.
13. The method of claim 1 , wherein the cancer is a sarcoma, bladder cancer or renal cancer.
14. The method of claim 1 , wherein the cancer is a renal cell carcinoma.
15. The method of claim 1 , wherein the cancer is a hematologic cancer.
16. The method of claim 15 , wherein the hematologic cancer is selected from acute myelogenous leukemia (AML), follicular lymphoma, acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), multiple myeloma (MM) or non-Hodgkin's lymphoma.
17. The method of claim 1 , wherein crystalline Form B of a compound having structure (I), or a zwitterionic form thereof, is administered to the mammal continuously.
18. The method of claim 1 , wherein crystalline Form B of a compound having structure (I), or a zwitterionic form thereof, is administered to the mammal once or twice daily for the first 21 days out of a 28-day cycle.
19. The method of claim 1 , wherein the cancer is MCL-1 dependent.
20. A method for treating a renal cancer in a mammal in need thereof, comprising administering to the mammal crystalline Form B of a compound having the following structure (I):
or a zwitterionic form thereof, in an amount of from about 1 mg to about 50 mg per day, wherein crystalline Form B is characterized by an x-ray powder diffraction pattern comprising at least three peaks at 2-theta angles selected from the group consisting of 4.8±0.2°, 10.8±0.2°, 13.7±0.2°, 14.9±0.2°, 20.0±0.2° and 24.6±0.2°.