Crystalline forms of PARP inhibitors

Patent metadata

Field	Value
Publication number	US-10150772-B2
Application number	US-201515529883-A
Country	US
Kind code	B2
Filing date	Nov 25, 2015
Priority date	Nov 26, 2014
Publication date	Dec 11, 2018
Grant date	Dec 11, 2018

Abstract

The present disclosure relates to crystalline forms of 4,5,6,7-tetrahydro-11-methoxy-2-[(4-methyl-1-piperazinyl)methyl]-1H-cyclopenta[a]pyrrolo[3,4-c]carbazole-1,3(2H)-dione, including salts forms and free base forms.

First claim

What is claimed:

1. A crystalline form of 4,5,6,7-tetrahydro-11-methoxy-2-[(4-methyl-1-piperazinyl)methyl]-1H-cyclopenta[a]pyrrolo[3,4-c]carbazole-1,3(2H)-dione (Compound A)

that is
Compound A, glycolate salt hydrate Form A 1 ;
Compound A, L-malate salt Form A 1 ; or
Compound A, L-pyroglutamate salt Form A 1 .

2. The crystalline form of claim 1 that is Compound A, glycolate salt hydrate Form A 1 .

3. The crystalline form of claim 2 , characterized by an X-ray powder diffraction pattern having at least three peaks selected from the group consisting of 8.2, 8.7, 13.8, 14.9, 16.4, 17.5, 18.2, 18.5, 20.2, 20.6, 21.2, 21.4, 23.0, 24.6, 27.8, 29.9, 30.1, and 30.5 degrees two theta±0.2 degrees 2-theta.

4. The crystalline form of claim 2 , further characterized by an X-ray powder diffraction pattern substantially as depicted in FIG. 9 or FIG. 10 .

5. The crystalline form of claim 2 , further characterized by a DSC substantially as depicted in FIG. 11 .

6. The crystalline form of claim 2 , further characterized by a DVS substantially as depicted in FIG. 12 .

7. The crystalline form of claim 1 that is Compound A, L-malate salt Form A 1 .

8. The crystalline form of claim 7 , characterized by an X-ray powder diffraction pattern having at least three peaks selected from the group consisting of 8.6, 9.2, 10.1, 10.4, 11.7, 11.9, 14.7, 15.3, 15.6, 17.2, 17.8, 18.5, 20.3, 20.7, 21.2, 22.4, 23.5, 24.3, and 27.0±0.2 degrees 2-theta.

9. The crystalline form of claim 7 , further characterized by an X-ray powder diffraction pattern substantially as depicted in FIG. 14 or FIG. 15 .

10. The crystalline form of claim 5 , further characterized by a DSC substantially as depicted in FIG. 16 .

11. The crystalline form of claim 7 , further characterized by a DVS substantially as depicted in FIG. 17 .

12. The crystalline form of claim 1 that is Compound A, L-pyroglutamate salt Form A 1 .

13. The crystalline form of claim 12 , characterized by an X-ray powder diffraction pattern having at least three peaks selected from the group consisting of 6.0, 9.6, 10.3, 10.5, 11.0, 12.0, 13.2, 15.0, 16.7, 17.5, 17.8, 18.0, 19.0, 20.8, 21.0, 21.1, 22.0, 22.1, 23.1, 23.4, 23.5, 24.8, and 26.6±0.2 degrees 2-theta.

14. The crystalline form of claim 12 , further characterized by an X-ray powder diffraction pattern substantially as depicted in FIG. 21 or FIG. 22 .

15. The crystalline form of claim 12 , further characterized by a DSC substantially as depicted in FIG. 23 .

16. The crystalline form of claim 12 , further characterized by a DVS substantially as depicted in FIG. 24 .

17. A pharmaceutical composition comprising the crystalline form of claim 1 , and at least one pharmaceutically acceptable excipient.

18. A method of treating cancer in a patient comprising administering to the patient a crystalline form of 4,5,6,7-tetrahydro-11-methoxy-2-[(4-methyl-1-pyrrolo[3,4-c]carbazole-1,3(2H)-dione (Compound A) according to claim 1 , wherein the cancer is breast cancer or ovarian cancer.

Assignees

• Cephalon Inc

Inventors

• Bierlmaier Stephen J
• Haltiwanger Ralph C
• Jacobs Martin J

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• C07C57/15

  Fumaric acid · CPC title

• C07D487/04 Primary

  Ortho-condensed systems · CPC title

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• A61P15/00

  Drugs for genital or sexual disorders (for disorders of sex hormones A61P5/24); Contraceptives · CPC title