CRYSTALS OF THIADIAZOLE DERIVATIVE DPP-IV INHIBITORS AND USES THEREOF

• US 20180334466A1
• Filed: 11/24/2016
• Published: 11/22/2018
• Est. Priority Date: 11/27/2015
• Status: Active Grant

• Current Assignee: Centaurus Biopharma Co., Ltd., Chia Tai Tianqing Pharmaceutical Group Co. Ltd. (SINO Biopharmaceutical Limited)
• Original Assignee: Centaurus Biopharma Co., Ltd., Chia Tai Tianqing Pharmaceutical Group Co. Ltd. (SINO Biopharmaceutical Limited)
• Inventors: Peng, Yan, Liu, Fei, Chen, Zhilin, Zhang, Yayu, Hu, Zhongyuan, Jiang, Jinfeng
• Granted Patent: US 10,450,328 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 31/522 having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: C07B 2200/13 Crystalline forms, e.g. polymorphs
• CPC Class Codes: C07D 519/00 Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00

Abstract

The present invention belongs to the field of drug crystals, relates to crystals of thiadiazole derivative DPP-IV inhibitors, and in particular relates to A and B type crystals of the compound as shown in formula 7. The crystals of the present invention have excellent stability. For example, under high temperature, high humidity or light test conditions, the material contents associated with the crystal of the compound of formula 7 do not change significantly. In addition, the crystal of the present invention also has a very good powder flowability and satisfies the requirements of drug preparation and production.

Claims

1. A crystalline Form A of the compound represented by Formula 7,

2. The crystalline Form A according to claim 1, having diffraction peaks at about 6.54, 8.27, 8.67, 9.16, 9.55, 11.68, 12.17, 12.98, 16.23, 18.15 and 18.91 degrees 2θ

.

3. The crystalline Form A according to claim 2, having diffraction peaks at about 6.54, 8.27, 8.67, 9.16, 9.55, 10.80, 11.68, 12.17, 12.98, 14.35, 15.05, 15.64, 16.23, 16.73, 17.31, 18.15, 18.91, 19.43, 20.23, 20.79, 21.36, 23.25, 23.96, 24.53, 25.05, 26.54, 28.43, 29.63 and 30.19 degrees 2θ

.

4. The crystalline Form A according to claim 1, having a powder X-ray diffraction pattern substantially as shown in FIG. 1.

9. A crystalline composition, wherein the crystalline Form A according to claim 1 accounts for 50% or more, preferably 80% or more, more preferably 90% or more, and most preferably 95% or more by weight of the crystalline composition.

10. A pharmaceutical composition, comprising the crystalline Form A according to claim 1, and pharmaceutically acceptable adjuvant(s).

13. A method for treating a disease benefiting from DPP-IV inhibition, comprising administering to a subject in need thereof the crystalline Form A according to claim 1;

preferably, the disease is diabetes.

17. A pharmaceutical composition, comprising the crystalline composition according to claim 9, and pharmaceutically acceptable adjuvant(s).

20. A method for treating a disease benefiting from DPP-IV inhibition, comprising administering to a subject in need thereof the crystalline composition according to claim 9;

preferably, the disease is diabetes.

21. A method for treating a disease benefiting from DPP-IV inhibition, comprising administering to a subject in need thereof the pharmaceutical composition according to claim 10;

preferably, the disease is diabetes.

5. A crystalline Form B of the compound represented by Formula 7,

6. The crystalline Form B according to claim 5, having diffraction peaks at about 4.86, 6.24, 7.88, 9.48, 10.54, 12.16, 15.82, 17.16, 17.76, 20.94 and 23.70 degrees 2θ

.

7. The crystalline Form B according to claim 6, having diffraction peaks at about 4.86, 6.24, 7.88, 9.48, 10.54, 12.16, 12.54, 14.00, 14.68, 15.30, 15.82, 17.16, 17.76, 18.16, 19.16, 19.58, 20.94, 22.96, 23.70, 24.76, 25.70, 26.44, 28.02, 28.96 and 29.38 degrees 2θ

.

8. The crystalline Form B according to claim 5, having a powder X-ray diffraction pattern substantially as shown in FIG. 2.

16. A crystalline composition, wherein the crystalline Form B according to claim 5 accounts for 50% or more, preferably 80% or more, more preferably 90% or more, and most preferably 95% or more by weight of the crystalline composition.

18. A pharmaceutical composition, comprising the crystalline Form B according to claim 5, and pharmaceutically acceptable adjuvant(s).

19. A pharmaceutical composition, comprising the crystalline composition according to claim 16, and pharmaceutically acceptable adjuvant(s).

22. A method for treating a disease benefiting from DPP-IV inhibition, comprising administering to a subject in need thereof the crystalline Form B according to claim 5;

preferably, the disease is diabetes.

23. A method for treating a disease benefiting from DPP-IV inhibition, comprising administering to a subject in need thereof the crystalline composition according to claim 16;

preferably, the disease is diabetes.

24. A method for treating a disease benefiting from DPP-IV inhibition, comprising administering to a subject in need thereof the pharmaceutical composition according to claim 18;

preferably, the disease is diabetes.

11-12. -12. (canceled)

14-15. -15. (canceled)