Crystal form and salt form of bromine domain protein inhibitor and preparation method therefor

Patent metadata

Field	Value
Publication number	US-12522600-B2
Application number	US-202117793588-A
Country	US
Kind code	B2
Filing date	Jan 19, 2021
Priority date	Jan 19, 2020
Publication date	Jan 13, 2026
Grant date	Jan 13, 2026

Abstract

A crystal form and salt form of a bromine domain protein inhibitor represented by formula (I), a preparation method therefor, and a use of the crystal form and salt form in the preparation of a drug for treating diseases mediated by BET protein.

First claim

The invention claimed is:

1 . A crystal form of a compound of formula (I), a pharmaceutically acceptable salt of a compound of formula (I) or a crystal form thereof:

wherein the crystal form is selected from the group consisting of:
a crystal form of the compound of formula (I), wherein the crystal form has characteristic diffraction peaks at the following 2θ:12.4°±0.2°, 14.5°±0.2°, 17.4°±0.2°, 18.5°±0.2°, 20.4°±0.2°, and 24.7°±0.2°, in an X-ray powder diffraction pattern;
a crystal form of a hydrochloride salt of the compound of formula (I), wherein the crystal form has characteristic diffraction peaks at the following 2θ:6.8°±0.2°, 8.4°±0.2°, 9.4°±0.2°, 10.2°±0.2°, and 16.8°±0.2°, in an X-ray powder diffraction pattern;
a crystal form of a hydrochloride salt of the compound of formula (I), wherein the crystal form has characteristic diffraction peaks at the following 2θ:8.7°±0.2°, 9.5°±0.2°, 10.5°±0.2°, 14.5°±0.2°, and 17.4°±0.2°, in an X-ray powder diffraction pattern;
a crystal form of a hydrochloride salt of the compound of formula (I), wherein the crystal form has characteristic diffraction peaks at the following 2θ:6.8°±0.2°, 9.5°±0.2°, 12.9°±0.2°, 20.5°±0.2°, and 24.6°±0.2°, in an X-ray powder diffraction pattern;
a crystal form of a sulfate salt of the compound of formula (I), wherein the crystal form has characteristic diffraction peaks at the following 2θ:13.5°±0.2°, 14.7°±0.2°, 18.6°±0.2°, 21.2°±0.2°, 23.0°±0.2°, and 24.1°±0.2°, in an X-ray powder diffraction pattern;
a crystal form of a phosphate salt of the compound of formula (I), wherein the crystal form has characteristic diffraction peaks at the following 2θ:10.1°±0.2°, 10.5°±0.2°, 19.0°±0.2°, 21.0°±0.2°, 22.7°±0.2°, and 24.0°±0.2°, in an X-ray powder diffraction pattern; and
a crystal form of a mesylate salt of the compound of formula (I), wherein the crystal form has characteristic diffraction peaks at the following 2θ:8.8°±0.2°, 10.1°±0.2°, 17.7°±0.2°, 18.0°±0.2°, 24.1°±0.2°, and 24.8°±0.2°, in an X-ray powder diffraction pattern;
and wherein the pharmaceutically acceptable salt of the compound of formula (I) is selected from the group consisting of: a hydrochloride salt of the compound of formula (I), a sulfate salt of the compound of formula (I), a phosphate salt of the compound of formula (I), and a mesylate salt of the compound of formula (I).

2 . The crystal form of the compound of formula (I), the pharmaceutically acceptable salt of the compound of formula (I) or the crystal form thereof according to claim 1 ,
wherein the crystal form is the crystal form of the compound of formula (I), the crystal form has characteristic diffraction peaks at the following 2θ:6.6°±0.2°, 9.3°±0.2°, 12.4°±0.2°, 14.5°±0.2°, 16.6°±0.2°, 17.4°±0.2°, 18.5°±0.2°, 20.0°±0.2°, 20.4°±0.2°, and 24.7°±0.2°, in an X-ray powder diffraction pattern; or, the crystal form has characteristic diffraction peaks at the following 2θ:6.6°±0.2°,

No.
2θ (±0.2°)
Relative intensity (%)

1
6.6
20.0

2
9.3
16.2

3
12.4
63.4

4
14.5
100.0

5
14.7
27.5

6
15.2
10.2

7
16.6
21.1

8
17.4
32.4

9
18.5
99.2

10
20.0
25.3

11
20.4
45.0

12
21.5
20.9

13
21.8
8.1

14
22.5
21.8

15
23.3
8.0

16
23.7
26.4

17
24.7
36.7

18
25.2
26.9

19
26.9
11.1

20
29.3
15.5

21
29.7
14.8

22
30.3
12.5

or, the crystal form has an X-ray powder diffraction (XRPD) pattern with characteristics represented by the XRPD pattern shown in FIG. 1 .

3 . The crystal form of the compound of formula (I), the pharmaceutically acceptable salt of the compound of formula (I) or the crystal form thereof according to claim 1 , wherein the crystal form is a crystal form of the hydrochloride salt of the compound of formula (I); optionally, the crystal form is a hydrate; preferably, the hydrate is selected from the group consisting of a hemihydrate, a monohydrate, a dihydrate, a trihydrate and a tetrahydrate; further preferably, the hydrate is selected from the group consisting of a monohydrate, a dihydrate and a tetrahydrate; and most preferably, the hydrate is selected from the group consisting of a monohydrate and a tetrahydrate.

4 . The crystal form of the compound of formula (I), the pharmaceutically acceptable salt of the compound of formula (I) or the crystal form thereof according to claim 3 ,
wherein the crystal form is the crystal form of the hydrochloride salt of the compound of formula (I), the crystal form has characteristic diffraction peaks at the following 2θ: 6.8°±0.2°, 8.4°±0.2°, 9.4°±0.2°, 10.2°±0.2°, 14.4°±0.2°, 16.8°±0.2°, 20.5°±0.2°, and 24.7°±0.2°, in an X-ray powder diffraction pattern; or, the crystal form has characteristic diffraction peaks at the following 2θ:6.8°±0.2°, 8.4°±0.2°, 9.4°±0.2°, 10.2°±0.2°, 14.4°±0.2°, 16.8°±0.2°, 19.2°±0.2°, 20.5°±0.2°, 21.7°±0.2°, 23.3°±0.2°, and 24.7°±0.2°; or, the crystal form has the following XRPD pattern analysis data:

Assignees

• Chia Tai Tianqing Pharmaceutical Group Co Ltd
• Shouyao Holdings Beijing Co Ltd

Inventors

• Xu Wenwei
• Shan Zhenliang
• Zhang Yingya
• Zhang Guoliang
• Ge Yun
• Zhang Aiming
• Zhang Xiquan

Classifications

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• A61P35/02

  specific for leukemia · CPC title

• A61K31/444

  containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone · CPC title

• C07C309/04

  containing only one sulfo group · CPC title

• C07D471/04 Primary

  Ortho-condensed systems · CPC title