Salt and crystal form of steroid derivative regulator

Patent metadata

Field	Value
Publication number	US-12590118-B2
Application number	US-202017597919-A
Country	US
Kind code	B2
Filing date	Aug 5, 2020
Priority date	Aug 7, 2019
Publication date	Mar 31, 2026
Grant date	Mar 31, 2026

Abstract

The present invention relates to a steroid derivative regulator, in particular to a compound of formula (I), a salt and crystal form thereof, a preparation method therefor, a pharmaceutical composition containing a therapeutically effective amount of the crystal form, and an application thereof as a GABAA receptor regulator in treatment of depression, convulsions, Parkinsonism and nervous system diseases.

First claim

What is claimed is:

1 . A crystal form of formula (VI), having the following structure:

wherein x is 0, the crystal form is crystal form I of free base, the X-ray powder diffraction pattern thereof has any 3 to 11 of the diffraction peaks at 2θ (±0.2°) of 16.7, 12.6, 17.4, 7.3, 20.2, 20.6, 11.9, 11.1, 23.9, 21.9 and 38
or,
wherein x is 0, the crystal form is crystal form II of free base, the X-ray powder diffraction pattern thereof has diffraction peaks at 2θ (±0.2°) of 11.7, 13.4, 13.6, 16.6 and 18.9;
or,
wherein x is 0, the crystal form is crystal form III of free base, the X-ray powder diffraction pattern thereof has diffraction peaks at 2θ (±0.2°) of 10.0, 11.7, 13.7, 16.6, 18.9 and 19.2:
or,
wherein M is methanesulfonic acid, x is 1, the X-ray powder diffraction pattern thereof has diffraction peaks at 2θ (±0.2°) of 12.5, 13.5, 194 and 19.9.

2 . The crystal form according to claim 1 , wherein,
the DSC spectrum of the crystal form I of free base has an endothermic peak at 151.4±0.5° C.; or, the DSC spectrum of the crystal form II of free base has an endothermic peak at 193.5±0.5° C.; or, the DSC spectrum of the crystal form III of free base has an endothermic peak at 206.4±0.5° C.

3 . The crystal form according to claim 1 , wherein the crystal form is crystal form I of free base and the X-ray powder diffraction pattern of the crystal form comprises any 5 to 8 or 6 to 8 of the diffraction peaks.

4 . The crystal form according to claim 1 , wherein the crystal form is crystal form I of free base and the X-ray powder diffraction pattern of the crystal form comprises any 3, 6, 8, 10 or 11 of the diffraction peaks.

5 . The crystal form according to claim 1 , wherein
the crystal form is crystal form I of free base and the X-ray powder diffraction pattern of the crystal form has diffraction peaks at 2θ (±0.2°) of 16.7, 12.6 and 17.4; the crystal form is crystal form II of free base and the X-ray powder diffraction pattern further has diffraction peaks at 2θ (±0.2°) of 9.5, 10.1, 14.7 and 19.3; the crystal form is crystal form III of free base and the X-ray powder diffraction pattern further has diffraction peaks at 2θ (±0.2°) of 13.4, 19.6, 20.6, 20.9, 22.0, 22.7, 23.4 and 25.6; or the X-ray powder diffraction pattern of the methanesulfonic acid crystal form further has diffraction peaks at 2θ (±0.2°) of 15.1, 15.8, 16.5, 17.3, 18.7 and 23.1.

6 . The crystal form according to claim 5 , wherein
the crystal form is crystal form I of free base and the X-ray powder diffraction pattern of the crystal form further comprises one or more diffraction peaks at 2θ (±0.2°) of 7.3, 20.2, 20.6, 11.9, 11.1, 23.9, 21.9 and 38.4; the crystal form is crystal form II of free base and the X-ray powder diffraction pattern further has diffraction peaks at 2θ (±0.2°) of 19.6, 20.6, 20.9, 21.6, 22.1, 22.5, 22.7 and 24.4; or the crystal form is crystal form of methanesulfonic acid and the X-ray powder diffraction pattern further has diffraction peaks at 2θ (±0.2°) of 11.1, 11.5, 13.9, 18.5, 213, 21.7, 26.5 and 28.9.

7 . The crystal form according to claim 1 , wherein the crystal form is crystal form I of free base and the X-ray powder diffraction pattern of the crystal form has diffraction peaks at 2θ (±0.2°) of 16.7, 12.6, 17.4, 7.3, 20.2 and 20.6.

8 . The crystal form according to claim 1 , wherein the crystal form is crystal form I of free base and the X-ray powder diffraction pattern of the crystal form has diffraction peaks at 2θ (±0.2°) of 16.7, 12.6, 17.4, 73, 20.2, 20.6, 11.9 and 11.1.

9 . The crystal form according to claim 1 , wherein the crystal form is crystal form I of free base and the X-ray powder diffraction pattern of the crystal form has diffraction peaks at 2θ (±0.2°) of 16.7, 12.6, 17.4, 7.3, 20.2, 20.6, 11.9, 11.1, 23.9 and 21.9.

10 . The crystal form according to claim 1 , wherein the crystal form is crystal form I of free base, and the X-ray powder diffraction pattern of the crystal form has diffraction peaks at 2θ (±0.2°) of 16.7, 12.6, 17.4, 7.3, 20.2, 20.6, 11.9, 11.1, 23.9, 21.9 and 38.4.

11 . The crystal form according to claim 1 , wherein
the crystal form is crystal form I of free base and the X-ray powder diffraction pattern of the crystal form is substantially as shown in FIG. 1 ; the crystal form is crystal form II of free base and the X-ray powder diffraction pattern thereof is substantially as shown in FIG. 3 ; the crystal form is crystal form III of free base and the X-ray powder diffraction pattern thereof is substantially as shown in FIG. 5 ; or the crystal form is crystal form of methanesulfonic acid and the X-ray powder diffraction pattern thereof is substantially as shown in FIG. 7 .

12 . A pharmaceutical composition, comprising a therapeutically effective amount of the crystal form of the compound of formula (VI) according to claim 1 , and one or more pharmaceutically acceptable carriers.

13 . A crystal form of a compound of formula (VI), having the following structure,

wherein
x is 0, the crystal form is crystal form I of free base and the X-ray powder diffraction pattern thereof has diffraction peaks at 2θ (±0.2°) of 16.7, 12.6 and 14.6;
the crystal form I of free base has diffraction peaks at 2θ (±0.2°) of 7.3, 13.2, 17.4, 19.4, 20.2 and 20.6; or
the crystal form I of free base has diffraction peaks at 2θ (±0.2°) of 9.2, 11.1, 11.9, 19.6, 22.3 and 25.5.

14 . A pharmaceutical composition, comprising a therapeutically effective amount of the crystal form of the compound of formula (VI) according to claim 13 , and one or more pharmaceutically acceptable carriers.

Assignees

• Shanghai Hansoh Biomedical Co Ltd
• Jiangsu Hansoh Pharmaceutical Group Co Ltd

Inventors

• Li Zongbin
• Kuang Yuanzhuo
• Guo Linsong

Classifications

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• A61P25/00 Primary

  Drugs for disorders of the nervous system · CPC title

• A61K31/58

  containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin (digitoxin {A61K31/7048}) · CPC title

• C07J43/003 Primary

  not condensed · CPC title

• C07D403/08

  linked by a carbon chain containing alicyclic rings · CPC title