Crystal form of five-membered n heterocyclic compound, and application thereof

Patent metadata

Field	Value
Publication number	US-12384745-B2
Application number	US-202017763114-A
Country	US
Kind code	B2
Filing date	Sep 28, 2020
Priority date	Sep 29, 2019
Publication date	Aug 12, 2025
Grant date	Aug 12, 2025

Abstract

Disclosed are a crystalline form of a five-membered N heterocyclic compound, particularly, a crystalline form of a compound as represented by formula I, and an application of the crystalline form in preparation of a medication for preventing or treating a disease benefiting from inhibition of capsid protein assembly.

First claim

The invention claimed is:

1. A crystal of a compound of formula I,

wherein the crystal has characteristic diffraction peaks in an X-ray powder diffraction pattern at the following 20 angles: 8.25±0.20°, 10.10±0.20°, 14.46±0.20°, 15.48±0.20° and 18.97±0.20°.

2. The crystal of the compound of formula I according to claim 1 , wherein the XRPD pattern of the crystal is as shown in FIG. 1 .

3. The crystal of the compound of formula I according to claim 1 , wherein the crystal has a DSC curve having an endothermic peak at 227.34±5° C.

4. A crystalline form composition, wherein the crystal of the compound of formula I according to claim 1 accounts for 50% or more of the weight of the crystalline form composition.

5. A pharmaceutical composition, comprising a therapeutically effective amount of the crystal of the compound of formula I according to claim 1 .

6. The crystal of the compound of formula I according to claim 1 , wherein the crystal has characteristic diffraction peaks in an X-ray powder diffraction pattern at the following 20 angles: 8.25±0.20°, 9.46±0.20°, 10.10±0.20°, 14.46±0.20°, 15.48±0.20°, 18.97±0.20°, 20.33±0.20° and 22.02±0.20°.

7. The crystal of the compound of formula I according to claim 1 , wherein the crystal has characteristic diffraction peaks in an X-ray powder diffraction pattern at the following 20 angles: 8.25±0.20°, 9.46±0.20°, 10.10±0.20°, 14.46±0.20°, 15.48±0.20°, 18.97±0.20°, 20.33±0.20°, 20.80±0.20°, 21.67±0.20°, 22.02±0.20°, 24.37±0.20°, 26.37±0.20° and 30.77±0.20°.

8. The crystal of the compound of formula I according to claim 1 , wherein the crystal has characteristic diffraction peaks in an X-ray powder diffraction pattern at the following 20 angles: 8.25±0.20°, 9.46±0.20°, 10.10±0.20°, 14.46±0.20°, 15.48±0.20°, 18.97±0.20°, 20.33±0.20°, 20.80±0.20°, 21.67±0.20°, 22.02±0.20°, 22.88±0.20°, 23.93±0.20°, 24.37±0.20°, 24.97±0.20°, 26.37±0.20°, 28.68±0.20° and 30.77±0.20°.

9. The crystalline form composition according to claim 4 , wherein the crystal of the compound of formula I according to claim 1 accounts for 80% or more of the weight of the crystalline form composition.

10. The crystalline form composition according to claim 4 , wherein the crystal of the compound of formula I according to claim 1 accounts for 90% or more of the weight of the crystalline form composition.

11. The crystalline form composition according to claim 4 , wherein the crystal of the compound of formula I according to claim 1 accounts for 95% or more of the weight of the crystalline form composition.

12. A pharmaceutical composition, comprising a therapeutically effective amount of the crystalline form composition according to claim 5 .

13. A method for treating a disease benefiting from the inhibition of capsid protein assembly, comprising administering to a mammal in need of such treatment a therapeutically effective amount of the crystal of the compound of formula I according to claim 1 , wherein the disease benefiting from the inhibition of capsid protein assembly is a disease caused by hepatitis B virus infection.

14. A method for treating a disease benefiting from the inhibition of capsid protein assembly, comprising administering to a mammal in need of such treatment a therapeutically effective amount of the crystalline form composition according to claim 4 , wherein the disease benefiting from the inhibition of capsid protein assembly is a disease caused by hepatitis B virus infection.

15. A method for treating a disease benefiting from the inhibition of capsid protein assembly, comprising administering to a mammal in need of such treatment a therapeutically effective amount of the pharmaceutical composition according to claim 5 , wherein the disease benefiting from the inhibition of capsid protein assembly is a disease caused by hepatitis B virus infection.

16. A method for treating hepatitis B virus infection, comprising administering to a mammal in need of such treatment a therapeutically effective amount of the crystal of the compound of formula I according to claim 1 .

Assignees

• Chia Tai Tianqing Pharmaceutical Group Co Ltd

Inventors

• Wang Pujun
• Guo Meng
• Hu Mingtong
• Wu Jie
• Ao Wangwei
• Zhang Yinsheng

Classifications

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• A61K31/40

  having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil · CPC title

• A61P31/20

  for DNA viruses · CPC title

• C07D207/34 Primary

  with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms · CPC title