# US 11,111,233 B2 · Amino pyrimidine compound for inhibiting protein tyrosine kinase activity

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 11,111,233 B2
- Document ID: US11111233B2
- Status: Granted
- Kind: B2
- Application number: 16/256,203
- Filed: 2019-01-24
- Published: 2019-05-23
- Granted: 2021-09-07
- Earliest claimed: 2016-07-26
- Assignees: Shenzhen TargetRx, Inc.
- Applicants: Shenzhen TargetRx, Inc.
- Inventors: Yihan Wang; Xingye Ren; Jian Jin; Huanyin Li; Yixin Ai
- Web page: https://patentgrep.com/patent/US11111233B2

## CPC

- C07D 403/04: directly linked by a ring-member-to-ring-member bond
- A61K 31/506: not condensed and containing further heterocyclic rings
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- C07D 401/14: containing three or more hetero rings
- C07D 413/04: directly linked by a ring-member-to-ring-member bond
- C07D 417/04: directly linked by a ring-member-to-ring-member bond
- C07D 471/04: Ortho-condensed systems
- C07D 487/04: Ortho-condensed systems
- 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

An amino pyrimidine compound for inhibiting protein tyrosine kinase activity, a pharmaceutical composition thereof, preparation therefor, and an application thereof. Specifically, an amino pyrimidine compound represented by formula (I), R1, R2, L, Y, R6, W, A, m, and n being defined in the specification, and a pharmaceutically acceptable salt, a stereoisomer, a solvent compound, a hydrate, a polymorphism, a prodrug, or an isotope variant thereof. The compound can be used for treating and/or preventing protein tyrosine kinase-related diseases such as cell proliferative diseases, cancers, and immune diseases.

## Claims

### Claim 1

A compound of formula (III):
wherein,
R1 is selected from H, halo, —CN, optionally substituted C1-C6 alkyl, optionally substituted C1-C6 haloalkyl, or optionally substituted C3-C6 carbocyclyl;
R2 is selected from optionally substituted C1-C6 alkoxy, or optionally substituted C1-C6 haloalkoxy;
-(L)n-R6 is:
Y is the following structure:
wherein R3, R4 and R5 are independently selected from H, halo, —CN, optionally substituted C1-C6 alkyl or optionally substituted C1-C6 haloalkyl;
ring A is selected from the following structures:
R11 is independently selected from H, halo, —CN, C1-C6 alkyl, or optionally substituted C3-C6 carbocyclyl, as long as the chemistry permits; or, two adjacent R11 could be taken together to form optionally substituted C5-C8 carbocyclyl, or optionally substituted 5- to 8-membered heterocyclyl;
or a pharmaceutically acceptable salt, a stereoisomer, a solvate, a hydrate, or an isotopically labeled compound thereof.

### Claim 2 (depends on 1)

The compound according to claim 1, wherein
R11 is independently selected from H, halo, or C1-C6 alkyl, or, two adjacent R11 could be taken together to form optionally substituted 5- to 8-membered heterocyclyl;
or a pharmaceutically acceptable salt, a stereoisomer, a solvate, a hydrate, or an isotopically labeled compound thereof.

### Claim 3

The compound of formula (III-a):
wherein,
R1 is selected from H, halo, —CN, optionally substituted C1-C6 alkyl, optionally substituted C1-C6 haloalkyl, or optionally substituted C3-C6 carbocyclyl;
R2 is selected from optionally substituted C1-C6 alkoxy or optionally substituted C1-C6 haloalkoxy;
R11 is selected from H, halo, optionally substituted C1-C6 alkyl, optionally substituted C1-C6 haloalkyl or optionally substituted C1-C6 alkoxy;
R12 is selected from H, or C1-C6 alkyl;
R13 is optionally substituted C1-C6 alkyl;
or a pharmaceutically acceptable salt, a stereoisomer, a solvate, a hydrate, or an isotopically labeled compound thereof.

### Claim 4

The compound of formula (III-c):
wherein,
R1 is selected from H, halo, —CN, optionally substituted C1-C6 alkyl, optionally substituted C1-C6 haloalkyl, optionally substituted C1-C6 alkoxy or optionally substituted C3-C6 carbocyclyl;
R2 is selected from optionally substituted C1-C6 alkoxy or optionally substituted C1-C6 haloalkoxy;
R7 is selected from H, or optionally substituted C1-C6 alkyl;
R11 is selected from H, halo, optionally substituted C1-C6 alkyl, optionally substituted C2-C6 alkenyl, optionally substituted C1-C6 haloalkyl or optionally substituted C1-C6 alkoxy;
R12 is independently selected from H, halo, —CN, —NO2, —OH, optionally substituted C1-C6 alkyl, optionally substituted C1-C6 haloalkyl, optionally substituted C2-C6 alkenyl, optionally substituted C2-C6 alkynyl, optionally substituted C3-C6 carbocyclyl, optionally substituted C1-C6 alkoxy, optionally substituted C1-C6 alkylthio or optionally substituted C1-C6 haloalkoxy, as long as the chemistry permits; wherein the said optionally substituted groups are optionally further substituted by 1, 2, 3, 4, 5, 6, 7, or 8 deuteriums;
R13 is selected from H, halo, optionally substituted C1-C6 alkyl, optionally substituted C2-C6 alkenyl, optionally substituted C1-C6 haloalkyl or optionally substituted C1-C6 alkoxy; wherein the said optionally substituted groups are optionally further substituted by 1, 2, 3, 4, 5, 6, 7, or 8 deuteriums;
or R12 and R13 could be taken together to form optionally substituted 5- to 8-membered heterocyclyl, or optionally substituted 5- to 10-membered heteroaryl;
R14 is selected from H, optionally substituted C1-C6 alkyl, or optionally substituted C1-C6 haloalkyl;
R15 is selected from —OH, —CN, —NO2, optionally substituted C1-C6 alkyl, optionally substituted C1-C6 alkoxy, or NR8R9; wherein R8 and R9 are each independently selected from H, optionally substituted C1-C6 alkyl, optionally substituted C1-C6 alkoxy, optionally substituted C1-C6 haloalkyl or optionally substituted C3-C6 carbocyclyl, or R8 and R9 together with the nitrogen atom to which they are attached form optionally substituted 4- to 6-membered heterocyclyl;
or a pharmaceutically acceptable salt, a stereoisomer, a solvate, a hydrate, or an isotopically labeled compound thereof.

### Claim 5 (depends on 1)

The Compound according to claim 1, which is selected from:
or a pharmaceutically acceptable salt thereof.

### Claim 6 (depends on 5)

The compound according to claim 5 having the following structure:
or a pharmaceutically acceptable salt thereof.

### Claim 7 (depends on 5)

The compound according to claim 5 having the following structure:
or a pharmaceutically acceptable salt thereof.

### Claim 8 (depends on 1)

The compound according to claim 1 having the following structure:
or a pharmaceutically acceptable salt thereof.

### Claim 9 (depends on 4)

The Compound according to claim 4, which is selected from:
or a pharmaceutically acceptable salt thereof.

### Claim 10 (depends on 1)

A pharmaceutical composition, comprising
a compound according to claim 1, or a pharmaceutically acceptable salt, a stereoisomer, a solvate, a hydrate, or an isotopically labeled compound thereof, and
a pharmaceutically acceptable excipient.

### Claim 11 (depends on 4)

A pharmaceutical composition, comprising
a compound according to claim 4, or a pharmaceutically acceptable salt, a stereoisomer, a solvate, a hydrate, or an isotopically labeled compound thereof, and
a pharmaceutically acceptable excipient.