Crystalline form of GnRH receptor antagonist and preparation method therefor

Patent metadata

Field	Value
Publication number	US-10787451-B2
Application number	US-201716348932-A
Country	US
Kind code	B2
Filing date	Nov 13, 2017
Priority date	Nov 14, 2016
Publication date	Sep 29, 2020
Grant date	Sep 29, 2020

Abstract

Provided are a crystalline form of a GnRH receptor antagonist and a preparation method therefor. Specifically, provided are a crystalline form I of 1-(4-(7-(2,6-difluorobenzyl)-3-((dimethylamino)methyl)-5-(6-methoxypyridazin-3-yl)-4,6-dicarbonyl-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-d]pyrimidin-2-yl)phenyl)-3-methoxy urea (a compound of formula I) and a preparation method, the use of same in a pharmaceutical composition and the use of the crystalline form I and the composition in the preparation of a drug for treating diseases associated with a GnRH receptor antagonist.

First claim

What is claimed is:

1. Crystal form I of a compound of formula (I), characterized by an X-ray powder diffraction spectrum comprising diffraction peaks at diffraction angles 2θ±0.2 of 5.56, 9.15, 9.79, 11.08, 19.59, 20.25 and 22.16:

2. The crystal form I according to claim 1 , wherein the X-ray powder diffraction spectrum comprises diffraction peaks at diffraction angles 2θ±0.2 of 5.56, 9.15, 9.79, 10.29, 11.08, 14.21, 16.61, 19.59, 20.25, 22.16 and 25.69.

3. The crystal form I according to claim 2 , wherein the X-ray powder diffraction spectrum comprises diffraction peaks at diffraction angles 2θ±0.2 of 5.22, 5.56, 9.15, 9.79, 10.29, 11.08, 13.38, 13.81, 14.21, 14.89, 16.61, 17.19, 18.47, 19.59, 20.25, 22.16, 23.32, 24.67, 25.69, 26.72, 28.73, 29.38, 31.78, 34.02 and 36.95.

4. A method for preparing the crystal form I of the compound of formula (I) according to claim 1 , comprising dissolving the compound of formula (I) in an organic solvent to precipitate a crystal, filtering, washing and drying the crystal to obtain the desired crystal form I, wherein the organic solvent is selected from the group consisting of an alcohol, ketone, ester, ether, a mixed solvent of an ether and an alcohol, and a mixed solvent of a ketone and water; and the alcohol solvent is selected from the group consisting of methanol, ethanol and isopropanol.

5. The crystal form I according to claim 1 , characterized by a DSC spectrum comprising a melting endothermic peak of 160° C. to 175° C.

6. A pharmaceutical composition comprising the crystal form I according to claim 1 , and one or more pharmaceutically acceptable carriers, diluents or excipients.

7. A method for preparing the crystal form I of the compound of formula (I) according to claim 1 , comprising adding the compound of formula (I) into an organic solvent to obtain a mixture; pulping the mixture; and filtering, washing and drying a crystal to obtain the desired crystal form I, wherein the organic solvent is selected from the group consisting of an alcohol, ketone, ester, ether, a mixed solvent of an ether and an alcohol, and a mixed solvent of a ketone and water; and the alcohol solvent is selected from the group consisting of methanol, ethanol, and isopropanol.

8. The method according to claim 4 , wherein the ketone solvent is acetone.

9. The method according to claim 4 , wherein the ester solvent is ethyl acetate.

10. The method according to claim 4 , wherein the ether solvent is tetrahydrofuran.

11. The method according to claim 4 , wherein the mixed solvent of the ether and the alcohol is tetrahydrofuran/ethanol or tetrahydrofuran/isopropanol.

12. The method according to claim 4 , wherein the mixed solvent of the ketone and water is acetone/water.

13. The method according to claim 7 , wherein the ketone solvent is acetone.

14. The method according to claim 7 , wherein the ester solvent is ethyl acetate.

15. The method according to claim 7 , wherein the ether solvent is tetrahydrofuran.

16. The method according to claim 7 , wherein the mixed solvent of the ether and the alcohol is tetrahydrofuran/ethanol or tetrahydrofuran/isopropanol.

17. The method according to claim 7 , wherein the mixed solvent of the ketone and water is acetone/water.

18. The crystal form I according to claim 5 , wherein the DSC spectrum comprises a melting endothermic peak of from 165° C. to 170° C.

19. The crystal form I according to claim 5 , wherein the DSC spectrum comprises a melting endothermic peak of 168.71° C.

20. A method for treating a disease associated with GnRH receptor antagonist, comprising administering to a subject in need thereof an effective amount of the pharmaceutical composition according to claim 6 , wherein the disease is selected from the group consisting of endometriosis, uterine leiomyoma, and prostate cancer.

Assignees

• Jiangsu Hengrui Medicine Co
• Suncadia Pharmaceuticals Co Ltd

Inventors

• Zhang Quanliang
• Jia Junlei
• Bian Lin
• Gao Xiaohui

Classifications

• C07D487/04 Primary

  Ortho-condensed systems · CPC title

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• A61P15/00 Primary

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

• A61K31/519

  ortho- or peri-condensed with heterocyclic rings · CPC title

• C07D473/28 Primary

  Oxygen atom · CPC title