Crystalline form of capsid protein assembly inhibitor containing N hetero five-membered ring, and application thereof

Patent metadata

Field	Value
Publication number	US-12378192-B2
Application number	US-202017764519-A
Country	US
Kind code	B2
Filing date	Sep 28, 2020
Priority date	Sep 29, 2019
Publication date	Aug 5, 2025
Grant date	Aug 5, 2025

Abstract

Disclosed by the present application is a crystalline form of a capsid protein assembly inhibitor containing an N hetero five-membered ring; specifically disclosed is the crystalline form of the compound of formula I; also comprised is an the application of said crystalline form in the preparation of a drug for preventing or treating diseases benefiting from the inhibition of capsid protein assembly.

First claim

The invention claimed is:

1. A crystalline form of a compound of formula I,

wherein the crystalline form has characteristic diffraction peaks in an X-ray powder diffraction (XRPD) pattern at three or more of the following 2θ: 9.21±0.20°, 16.47±0.20°, 18.11±0.20°, 24.48±0.20°, 26.79±0.20°, or
wherein the crystalline form has characteristic diffraction peaks in an XRPD pattern at three or more of the following 2θ: 14.09±0.20°, 15.81±0.20°, 17.40±0.20°, 18.81±0.20° and 22.91±0.2°.

2. The crystalline form of the compound of formula I according to claim 1 , wherein the crystalline form has characteristic diffraction peaks in an X-ray powder diffraction pattern at the following 2θ: 9.21±0.20°, 16.47±0.20°, 18.11±0.20°, 24.48±0.20° and 26.79±0.20°.

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

4. The crystalline form of the compound of formula I according to claim 2 , wherein the crystalline form has an endothermic peak in a DSC curve at 231.26±5° C.

5. The crystalline form of the compound of formula I according to claim 1 , wherein the crystalline form has characteristic diffraction peaks in an X-ray powder diffraction pattern at the following 2θ: 14.09±0.20°, 15.81±0.20°, 17.40±0.20°, 18.81±0.20° and 22.91±0.2°.

6. The crystalline form of the compound of formula I according to claim 5 , wherein the XRPD pattern of the crystalline form is shown in FIG. 3 .

7. The crystalline form of the compound of formula I according to claim 5 , wherein the crystalline form has an endothermic peak in a DSC curve at 225.05±5° C.

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

9. A pharmaceutical composition, comprising a therapeutically effective amount of the crystalline form of the compound of formula I according to claim 1 .

10. A method for treating a disease caused by hepatitis B virus infection, comprising administering to a mammal in need of such treatment a therapeutically effective amount of the crystalline form of the compound of formula I according to claim 1 .

11. The crystalline form of the compound of formula I according to claim 2 , wherein the crystalline form has characteristic diffraction peaks in an X-ray powder diffraction pattern at the following 2θ: 9.21±0.20°, 12.72±0.20°, 15.71±0.20°, 16.47±0.20°, 18.11±0.20°, 19.79±0.20°, 24.48±0.20° and 26.79±0.20°.

12. The crystalline form of the compound of formula I according to claim 2 , wherein the crystalline form has characteristic diffraction peaks in an X-ray powder diffraction pattern at the following 2θ: 9.21±0.20°, 10.44±0.20°, 12.72±0.20°, 15.06±0.20°, 15.71±0.20°, 16.47±0.20°, 18.11±0.20°, 19.79±0.20°, 20.46±0.20°, 24.48±0.20°, 26.79±0.20° and 31.46±0.20°.

13. The crystalline form of the compound of formula I according to claim 2 , wherein the crystalline form has characteristic diffraction peaks in an X-ray powder diffraction pattern at the following 2θ: 9.21±0.20°, 9.68±0.20°, 10.44±0.20°, 12.72±0.20°, 15.06±0.20°, 15.71±0.20°, 16.47±0.20°, 18.11±0.20°, 19.79±0.20°, 20.46±0.20°, 24.48±0.20°, 26.02±0.20°, 26.79±0.20°, 27.67±0.20° and 31.46±0.20°.

14. The crystalline form of the compound of formula I according to claim 2 , wherein the crystalline form has characteristic diffraction peaks in an X-ray powder diffraction pattern at the following 2θ: 4.86±0.20°, 9.21±0.20°, 9.68±0.20°, 10.44±0.20°, 12.47±0.20°, 12.72±0.20°, 15.06±0.20°, 15.71±0.20°, 16.47±0.20°, 18.11±0.20°, 18.74±0.20°, 19.19±0.20°, 19.79±0.20°, 20.46±0.20°, 20.94±0.20°, 21.65±0.20°, 21.96±0.20°, 23.12±0.20°, 24.48±0.20°, 26.02±0.20°, 26.79±0.20°, 27.67±0.20°, 29.36±0.20°, 31.46±0.20° and 34.17±0.20°.

15. The crystalline form of the compound of formula I according to claim 5 , wherein the crystalline form has characteristic diffraction peaks in an X-ray powder diffraction pattern at the following 2θ: 8.45±0.20°, 13.35±0.20°, 14.09±0.20°, 14.90±0.20°, 15.81±0.20°, 17.40±0.20°, 18.81±0.20°, 19.64±0.20° and 22.91±0.20°.

16. The crystalline form of the compound of formula I according to claim 5 , wherein the crystalline form has characteristic diffraction peaks in an X-ray powder diffraction pattern at the following 2θ: 8.45±0.20°, 11.15±0.20°, 13.35±0.20°, 14.09±0.20°, 14.90±0.20°, 15.81±0.20°, 17.40±0.20°, 18.81±0.20°, 19.64±0.20°, 20.97±0.20°, 22.91±0.20°, 23.68±0.20° and 25.24±0.20°.

17. The crystalline form of the compound of formula I according to claim 5 , wherein the crystalline form has characteristic diffraction peaks in an X-ray powder diffraction pattern at the following 2θ: 8.45±0.20°, 11.15±0.20°, 13.35±0.20°, 14.09±0.20°, 14.90±0.20°, 15.81±0.20°, 17.40±0.20°, 18.81±0.20°, 19.64±0.20°, 20.25±0.20°, 20.97±0.20°, 21.42±0.20°, 22.91±0.20°, 23.68±0.20°, 25.24±0.20°, 27.72±0.20° and 30.00±0.20°.

18. The crystalline form of the compound of formula I according to claim 5 , wherein the crystalline form has characteristic diffraction peaks in an X-ray powder diffraction pattern at the following 2θ: 4.74±0.20°, 7.94±0.20°, 8.45±0.20°, 9.40±0.20°, 9.91±0.20°, 11.15±0.20°, 13.35±0.20°, 14.09±0.20°, 14.90±0.20°, 15.81±0.20°, 17.40±0.20°, 18.81±0.20°, 19.64±0.20°, 20.25±0.20°, 20.97±0.20°, 21.42±0.20°, 22.91±0.20°, 23.68±0.20°, 25.24±0.20°, 27.72±0.20° and 30.00±0.20°.

Assignees

• Chia Tai Tianqing Pharmaceutical Group Co Ltd

Inventors

• Lu Yin
• Guo Meng
• Hu Mingtong
• Li Yuan
• Ao Wangwei
• Zhang Yinsheng

Classifications

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• C07B2200/07

  Optical isomers · 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

• A61P31/20 Primary

  for DNA viruses · CPC title