# US 11,078,213 B2 · Thienopyrimidine compound, preparation method thereof, pharmaceutical composition and application thereof

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- Number: US 11,078,213 B2
- Document ID: US11078213B2
- Status: Granted
- Kind: B2
- Application number: 16/324,040
- Filed: 2017-09-28
- Published: 2019-07-11
- Granted: 2021-08-03
- Earliest claimed: 2016-08-09
- Assignees: Hongyun Biotech Co., Ltd.
- Applicants: Hongyun Biotech Co., Ltd.
- Inventors: Xianming Deng; Baoding Zhang; Shuang Liu; Chao Dong; Xihuan Sun; Xiaoxing Huang; Zhou Deng; Yunzhan Li; Yue Lu; Li Li; Zhiyu Hu
- Web page: https://patentgrep.com/patent/US11078213B2

## CPC

- C07D 495/04: Ortho-condensed systems
- A61K 31/519: ortho- or peri-condensed with heterocyclic rings
- A61K 31/5377: not condensed and containing further heterocyclic rings, e.g. timolol
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- A61P 35/04: specific for metastasis
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present invention relates to thienopyrimidine compound, preparation method thereof, pharmaceutical composition and use thereof, and in particular to a type of compounds having ALK and/or c-Met selective inhibitory activity, a method for the preparation thereof, a pharmaceutical composition comprising the same, and use of these compounds in the manufacture of a medicament for preventing or treating a disease associated with anaplastic lymphoma kinase in vivo, and in the manufacture of a medicament for preventing or treating a disease associated with angiogenesis or cancer metastasis, in particular in the manufacture of a medicament for preventing or treating tumor growth and metastasis.

## Claims

### Claim 1

A compound of Formula I
wherein:
R′ is H;
R1 is selected from the group consisting of:
A is a direct on or methylene;
X is NH, S or O;
R2 is selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.

### Claim 2 (depends on 1)

A compound according to claim 1, which is a compound of Formula IPQ
wherein,
R1 is selected from the group consisting of:
R2 is
or a pharmaceutically acceptable salt thereof.

### Claim 3 (depends on 1)

A compound according to claim 1, which is a compound of Formula IRS
wherein, R1 is selected from the group consisting of:
R2 is
or a pharmaceutically acceptable salt thereof.

### Claim 4 (depends on 1)

A compound according to claim 1, selected from:
No.
Structure
IA-1
IA-2
IA-3
IA-4
IA-5
IA-6
IB-1
IB-2
IB-3
IB-4
IB-5
IB-6
IB-7
IB-8
IB-9
IB-10
IB-11
IB-12
IB-13
IB-14
IB-15
IB-16
IB-17
IB-18
IB-19
IB-20
IB-21
IB-22
IB-23
IB-24
IB-25
IB-26
IB-28
IB-29
IB-30
IC-1
IC-2
IC-3
IC-4
ID-1
ID-2
ID-3
ID-4
ID-5
ID-6
IE-1
IE-2
IE-3
IE-4
IE-5
IE-6
IE-7
IE-8
IB-32
IB-34
IO-1
IO-3
IP-1
IP-3
IT-1
IT-3
IT-5
IU-1
IU-3
IF-1
IF-2
IF-3
IG-1
IG-2
IG-3
IG-4
IG-5
IG-6
IH-1
IH-2
IH-3
IH-4
IH-5
IH-6
IH-7
II-1
II-2
II-3
II-4
II-5
II-6
II-7
II-8
II-9
IJ-1
IJ-2
IJ-3
IJ-4
IJ-5
IJ-6
IL-1
IL-2
IL-3
IL-4
IM-1
IM-2
IM-3
IM-4
IN-1
IN-2
IN-3
IN-4
IN-5
IN-6
IN-7
IB-31
IB-33
IB-35
IO-2
IO-4
IP-2
IQ-1
IT-2
IT-4
IT-6
IU-2
or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof.

### Claim 5 (depends on 1)

A pharmaceutical composition comprising a compound according to claim 1 or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof and optionally a pharmaceutically acceptable excipient.

### Claim 6 (depends on 1)

A method for treating a disease associated with anaplastic lymphoma kinase accompanied by abnormal cell proliferation, morphological changes, hyperkinesia in vivo, wherein the disease is any one selected from the group consisting of anaplastic large cell lymphoma, and non-small cell lung cancer, in a subject in need of such treatment comprising administering to the subject an effective amount of a compound according to claim 1 or a pharmaceutically acceptable salt thereof.

### Claim 7 (depends on 4)

A pharmaceutical composition comprising a compound according to claim 4 or a pharmaceutically acceptable salt thereof and optionally a pharmaceutically acceptable excipient.

### Claim 8 (depends on 4)

A method for treating a disease associated with anaplastic lymphoma kinase accompanied by abnormal cell proliferation, morphological changes, hyperkinesia in vivo wherein the disease is any one selected from the group consisting of anaplastic large cell lymphoma, and non-small cell lung cancer, in a subject in need of such treatment comprising administering to the subject an effective amount of a compound according to claim 4 or a pharmaceutically acceptable salt thereof.

### Claim 9 (depends on 5)

A method for treating a disease associated with anaplastic lymphoma kinase accompanied by abnormal cell proliferation, morphological changes, hyperkinesia in vivo wherein the disease is any one selected from the group consisting of anaplastic large cell lymphoma, and non-small cell lung cancer, in a subject in need of such treatment comprising administering to the subject an effective amount of a pharmaceutical composition according to claim 5.

### Claim 10 (depends on 1)

A compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein the pharmaceutically acceptable salt is an inorganic acid salt or an organic acid salt, wherein the inorganic acid salt is selected from hydrochloride, hydrobromide, hydroiodide, nitrate, bicarbonate, carbonate, sulfate, phosphate, and wherein the organic acid salt is selected from formate, acetate, propionate, benzoate, maleate, fumarate, succinate, tartrate, citrate, ascorbate, α-ketoglutarate, trifluoro acetate, α-glycero phosphate, alkyl sulfonate or aryl sulfonate.

### Claim 11 (depends on 2)

A compound according to claim 2, or a pharmaceutically acceptable salt thereof, wherein the pharmaceutically acceptable salt is an inorganic acid salt or an organic acid salt, wherein the inorganic acid salt is selected from hydrochloride, hydrobromide, hydroiodide, nitrate, bicarbonate, carbonate, sulfate or phosphate, and wherein the organic acid salt is selected from formate, acetate, propionate, benzoate, maleate, fumarate, succinate, tartrate, citrate, ascorbate, α-ketoglutarate, trifluoro acetate, α-glycero phosphate, alkyl sulfonate or aryl sulfonate.

### Claim 12 (depends on 3)

A compound according to claim 3, or a pharmaceutically acceptable salt thereof, wherein the pharmaceutically acceptable salt is an inorganic acid salt or an organic acid salt, wherein the inorganic acid salt is selected from hydrochloride, hydrobromide, hydroiodide, nitrate, bicarbonate, carbonate, sulfate or phosphate, and wherein the organic acid salt is selected from formate, acetate, propionate, benzoate, maleate, fumarate, succinate, tartrate, citrate, ascorbate, α-ketoglutarate, trifluoro acetate, α-glycero phosphate, alkyl sulfonate or aryl sulfonate.

### Claim 13 (depends on 4)

A compound according to claim 4, or a pharmaceutically acceptable salt thereof, wherein the pharmaceutically acceptable salt is an inorganic acid salt or an organic acid salt, wherein the inorganic acid salt is selected from hydrochloride, hydrobromide, hydroiodide, nitrate, bicarbonate, carbonate, sulfate or phosphate, and wherein the organic acid salt is selected from formate, acetate, propionate, benzoate, maleate, fumarate, succinate, tartrate, citrate, ascorbate, α-ketoglutarate, trifluoro acetate, α-glycero phosphate, alkyl sulfonate or aryl sulfonate.