# US 2025/0145641 A1 · Fused bicyclic derivative, pharmaceutically acceptable salt, crystal form thereof and preparation method therefor

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- Number: US 2025/0145641 A1
- Document ID: US20250145641A1
- Status: Published application
- Kind: A1
- Application number: 18/691,152
- Filed: 2022-09-16
- Published: 2025-05-08
- Earliest claimed: 2021-09-17
- Assignees: Jiangsu Hengrui Pharmaceuticals Co., Ltd.; Shanghai Hengrui Pharmaceutical Co., Ltd.
- Applicants: Jiangsu Hengrui Pharmaceuticals Co., Ltd.; Shanghai Hengrui Pharmaceutical Co., Ltd.
- Inventors: Tingting SHANG; Miaomiao ZHAO; Junran YANG; Zhenxing DU; Lin WANG; Qiyun SHAO; Jun FENG; Feng HE
- Web page: https://patentgrep.com/patent/US20250145641A1

## CPC

- A61P 35/00: Antineoplastic agents
- 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
- A61K 31/519: ortho- or peri-condensed with heterocyclic rings
- C07C 53/10: Salts thereof
- C07C 59/255: Tartaric acid
- C07C 309/04: containing only one sulfo group
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS

## Abstract

Provided are a fused bicyclic derivative, a pharmaceutically acceptable salt, a crystal form thereof and a preparation method therefor. Specifically, provided are a hydrochloride, a mesylate, an acetate and a tartrate of the compound of formula (I), and a preparation method therefor and a crystal form thereof.

## Claims

### Claim 1

A pharmaceutically acceptable salt of a compound of formula I, wherein the pharmaceutically acceptable salt is selected from hydrochloride, methanesulfonate, acetate, or tartrate,

### Claim 2 (depends on 1)

The pharmaceutically acceptable salt of the compound of formula I according to claim 1, wherein the molar ratio of the compound of formula I to the acid radical is selected from 1:2 to 3:1.

### Claim 3

A crystal form A of hydrochloride of a compound of formula I, which has an X-ray powder diffraction pattern comprising characteristic peaks at 2θ angles of 10.6, 11.4, 13.6, 17.6, 18.2, and 18.8, and the 2θ angle has an error range of ±0.2;

### Claim 4 (depends on 3)

The crystal form A of the hydrochloride of the compound of formula I according to claim 3, which has the X-ray powder diffraction pattern comprising characteristic peaks at 2θ angles of 10.6, 11.4, 13.6, 15.0, 17.1, 17.6, 18.2, 18.8, 20.5, 22.0, and 27.5.

### Claim 5 (depends on 3)

The crystal form A of the hydrochloride of the compound of formula I according to claim 3, which has the X-ray powder diffraction pattern comprising characteristic peaks at 2θ angles of 10.6, 11.0, 11.4, 12.3, 13.6, 14.3, 15.0, 17.1, 17.6, 18.2, 18.8, 20.2, 20.5, 21.3, 22.0, 23.0, 23.7, 24.4, 25.0, 25.4, 26.1, 26.6, 27.5, 28.3, 28.7, 29.4, 30.4, 31.4, 31.9, 32.2, 33.3, 34.9, 38.1, 39.9, and 41.0.

### Claim 6 (depends on 3)

The crystal form A of the hydrochloride of the compound of formula I according to claim 3, which has the X-ray powder diffraction pattern as shown in FIG. 2.

### Claim 7

A crystal form A of methanesulfonate of a compound of formula I, which has an X-ray powder diffraction pattern comprising characteristic peaks at 2θ angles of 9.1, 11.0, 14.9, 16.2, and 17.0;
or, a crystal form α of acetate of the compound of formula I, which has an X-ray powder diffraction pattern comprising characteristic peaks at 2θ angles of 8.9, 11.0, 14.9, 15.7, 17.0, and 19.7;
or, a crystal form I of tartrate of the compound of formula I, which has an X-ray powder diffraction pattern comprising characteristic peaks at 2θ angles of 7.9, 8.6, 10.0, 10.9, 11.7, 13.9, 14.2, 14.4, 15.3, 16.4, 17.4, 17.8, 19.0, 20.1, 21.2, 21.5, 22.3, 23.7, 24.0, 24.6, 25.1, 26.3, 27.7, 28.7, 29.3, 30.6, and 30.9;
the 2θ angle has an error range of ±0.2;

### Claim 8 (depends on 7)

The crystal form according to claim 7, wherein the crystal form A of the methanesulfonate of the compound of formula I has the X-ray powder diffraction pattern comprising characteristic peaks at 2θ angles of 9.1, 11.0, 14.9, 16.2, 17.0, 20.1, 20.9, 21.2, 24.3, and 27.4;
or, the crystal form α of the acetate of the compound of formula I has the X-ray powder diffraction pattern comprising characteristic peaks at 2θ angles of 8.9, 11.0, 14.9, 15.7, 17.0 19.1, 19.7, 20.4, 23.6, 23.9, and 27.2.

### Claim 9 (depends on 7)

The crystal form according to claim 7, wherein the crystal form A of the methanesulfonate of the compound of formula I has the X-ray powder diffraction pattern comprising characteristic peaks at 2θ angles of 9.1, 10.1, 11.0, 12.2, 13.6, 14.9, 15.4, 15.8, 16.2, 17.0, 18.0, 18.6, 19.3, 20.1, 20.9, 21.2, 22.2, 23.1, 23.6, 24.3, 24.5, 24.9, 25.0, 25.2, 26.0, 27.4, 27.7, 28.8, 29.4, 29.8, 30.2, 30.8, 31.3, 32.1, 32.8, and 33.8;
or, the crystal form α of the acetate of the compound of formula I has the X-ray powder diffraction pattern comprising characteristic peaks at 2θ angles of 8.9, 10.3. 11.0, 13.6, 14.9 15.7, 17.0, 18.1, 18.6, 19.1, 19.7, 20.4, 20.8, 21.3, 22.2, 23.6, 23.9, 24.9, 26.0, 27.2. 28.3, 28.7, 29.0, 30.8, 32.4, 33.6, 33.9, 34.5, 35.3, 36.4, and 38.4.

### Claim 10 (depends on 7)

The crystal form according to claim 7, wherein the crystal form A of the methanesulfonate of the compound of formula I has the X-ray powder diffraction pattern as shown in FIG. 3;
or, the crystal form α of the acetate of the compound of formula I has the X-ray powder diffraction pattern as shown in FIG. 4;
or, the crystal form I of the tartrate of the compound of formula I has the X-ray powder diffraction pattern as shown in FIG. 5.

### Claim at position 11

11-17. (canceled)

### Claim 18 (depends on 3)

A method for preparing the crystal form A of the hydrochloride of the compound of formula I according to claim 3, the method comprises: mixing the compound of formula I with an appropriate amount of a solvent and hydrochloric acid, and stirring for crystallization, the solvent being one or more than one of isopropanol, acetonitrile, water/ethanol, and isopropyl acetate.

### Claim 19 (depends on 7)

A method for preparing the crystal form according to claim 7, wherein a method for preparing the crystal form A of the methanesulfonate of the compound of formula I comprises: mixing the compound of formula I with an appropriate amount of a solvent and methanesulfonic acid, and stirring for crystallization, the solvent being one or more than one of isopropanol, acetonitrile, ethanol, water/ethanol, and isopropyl acetate;
or, a method for preparing the crystal form α of the acetate of the compound of formula I comprises: mixing the compound of formula I with an appropriate amount of a solvent and acetic acid, and stirring for crystallization, the solvent being one or more than one of isopropanol, acetonitrile, and water/ethanol;
or, a method for preparing the crystal form I of the tartrate of the compound of formula I comprises: mixing the compound of formula I with an appropriate amount of a solvent and tartaric acid, and stirring for crystallization, the solvent being one or more than one of isopropanol and water/ethanol.

### Claim at position 14

20-21. (canceled)

### Claim 22 (depends on 1)

A pharmaceutical composition comprising the following components:
(a) the pharmaceutically acceptable salt of the compound of formula I according to claim 1; and
(b) an optional pharmaceutically acceptable carrier, diluent, or excipient.

### Claim 23 (depends on 1)

A method for preparing a pharmaceutical composition, comprising a step of mixing:
(a) the pharmaceutically acceptable salt of the compound of formula I according to claim 1; and
(b) an optional pharmaceutically acceptable carrier, diluent, or excipient.

### Claim 24 (depends on 1)

A method for treating cancer in a subject in need thereof, comprising: administering the pharmaceutically acceptable salt of the compound of formula I according to claim 1 to the subject.

### Claim 25 (depends on 24)

The method according to claim 24, wherein the cancer is selected from ovarian cancer, breast cancer, prostate cancer, neuroglioma, spongiocytoma, gastric cancer, fallopian tube cancer, lung cancer, peritoneal tumor, melanoma, brain cancer, esophageal cancer, liver cancer, pancreatic cancer, colorectal cancer, lung cancer, kidney cancer, cervical cancer, skin cancer, neuroblastoma, sarcoma, bone cancer, uterine cancer, endometrial cancer, head and neck tumor, multiple myeloma, lymphoma, non-Hodgkin's lymphoma, non-small cell lung cancer, polycythemia vera, leukemia, thyroid tumor, bladder cancer, and gallbladder cancer.

### Claim 26 (depends on 3)

A method for treating cancer in a subject in need thereof, comprising:
administering the crystal form A of hydrochloride of the compound of formula I according to claim 3 to the subject.

### Claim 27 (depends on 26)

The method according to claim 26, wherein the cancer is selected from ovarian cancer, breast cancer, prostate cancer, neuroglioma, spongiocytoma, gastric cancer, fallopian tube cancer, lung cancer, peritoneal tumor, melanoma, brain cancer, esophageal cancer, liver cancer, pancreatic cancer, colorectal cancer, lung cancer, kidney cancer, cervical cancer, skin cancer, neuroblastoma, sarcoma, bone cancer, uterine cancer, endometrial cancer, head and neck tumor, multiple myeloma, lymphoma, non-Hodgkin's lymphoma, non-small cell lung cancer, polycythemia vera, leukemia, thyroid tumor, bladder cancer, and gallbladder cancer.

### Claim 28 (depends on 7)

A method for treating cancer in a subject in need thereof, comprising: administering the crystal form according to claim 7 to the subject.

### Claim 29 (depends on 28)

The method according to claim 28, wherein the cancer is selected from ovarian cancer, breast cancer, prostate cancer, neuroglioma, spongiocytoma, gastric cancer, fallopian tube cancer, lung cancer, peritoneal tumor, melanoma, brain cancer, esophageal cancer, liver cancer, pancreatic cancer, colorectal cancer, lung cancer, kidney cancer, cervical cancer, skin cancer, neuroblastoma, sarcoma, bone cancer, uterine cancer, endometrial cancer, head and neck tumor, multiple myeloma, lymphoma, non-Hodgkin's lymphoma, non-small cell lung cancer, polycythemia vera, leukemia, thyroid tumor, bladder cancer, and gallbladder cancer.