# US 2019/0169163 A1 · Quinoline derivative and use thereof

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- Number: US 2019/0169163 A1
- Document ID: US20190169163A1
- Status: Published application
- Kind: A1
- Application number: 16/266,000
- Filed: 2019-02-02
- Published: 2019-06-06
- Earliest claimed: 2016-08-09
- Inventors: JIANMING YIN
- Web page: https://patentgrep.com/patent/US20190169163A1

## CPC

- C07D 401/12: linked by a chain containing hetero atoms as chain links
- A61K 31/47: Quinolines; Isoquinolines
- A61K 31/4709: Non-condensed quinolines and containing further heterocyclic rings
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 35/00: Antineoplastic agents
- C07D 215/233: only one oxygen atom which is attached in position 4
- C07D 215/46: with hydrocarbon radicals, substituted by nitrogen atoms, attached to said nitrogen atoms
- C07D 215/48: Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- 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

Provided are a novel quinoline derivative, or a pharmaceutically acceptable salt, a hydrate, or a metabolite formed by metabolism in any form thereof, and use thereof in preparing a medicine for preventing and/or treating indications associated with angiogenesis. The quinoline derivative is an ideal and high-efficiency VEGFR inhibitor, and is able to be used to treat or prevent tumour growth and other metastasis growth diseases associated with angiogenesis.

## Claims

### Claim 1

A quinoline derivative having a structure represented by Formula (I), or a pharmaceutically acceptable salt, a hydrate, or a metabolite formed by metabolism in any form thereof,
wherein:
R1 is R5 or NHR5, wherein R5 is selected from cycloalkyl, heterocyclic and substituted heterocyclic;
R2 is selected from hydrogen, halogen, hydroxy, alkoxy and cyano;
R3 and R4 are independently selected from OR6, C(O)NH2 and C(O)NHR6, wherein R6 is C1-C6 alkyl or halogenated alkyl;
X is selected from NH and O;
non-exchangeable hydrogen is unsubstituted, or partially or fully substituted by deuterium in the quinoline derivative having the structure represented by Formula (I), or the pharmaceutically acceptable salt, the hydrate, or the metabolite formed by metabolism in any form thereof.

### Claim 2 (depends on 1)

The quinoline derivative, or the pharmaceutically acceptable salt, the hydrate, or the metabolite formed by metabolism in any form thereof according to claim 1, wherein R2 is Cl or F.

### Claim 3 (depends on 1)

The quinoline derivative, or the pharmaceutically acceptable salt, the hydrate, or the metabolite formed by metabolism in any form thereof according to claim 1, wherein R5 is cycloalkyl or halogenated cycloalkyl; or R5 is heterocycle containing N or O, which is unsubstituted or substituted by one or more substituents selected from halogen and C1-C6 alkyl, wherein carbon number of the cycloalkyl is 3 to 6.

### Claim 4 (depends on 3)

The quinoline derivative, or the pharmaceutically acceptable salt, the hydrate, or the metabolite formed by metabolism in any form thereof according to claim 3, wherein R5 is cycloalkyl having a carbon number of 3; or R5 is five- or six-membered unsaturated heterocycle containing 1 or 2 or 3 N, which is unsubstituted or substituted by one or two substituents selected from methyl and ethyl.

### Claim 5 (depends on 4)

The quinoline derivative, or the pharmaceutically acceptable salt, the hydrate, or the metabolite formed by metabolism in any form thereof according to claim 4, wherein R5 is five-membered unsaturated heterocycle containing 2 N, which is unsubstituted or substituted by one methyl.

### Claim 6 (depends on 1)

The quinoline derivative, or the pharmaceutically acceptable salt, the hydrate, or the metabolite formed by metabolism in any form thereof according to claim 1, wherein R6 is methyl or ethyl.

### Claim 7 (depends on 1)

The quinoline derivative, or the pharmaceutically acceptable salt, the hydrate, or the metabolite formed by metabolism in any form thereof according to claim 1, wherein the quinoline derivative is one of compounds represented by the following structural formulas,

### Claim 8

(canceled)

### Claim 9

(canceled)

### Claim 10 (depends on 1)

A medicine for preventing and/or treating indications associated with angiogenesis, containing the quinoline derivative, or the pharmaceutically acceptable salt, the hydrate, or the metabolite formed by metabolism in any form thereof according to claim 1.

### Claim 11 (depends on 1)

The quinoline derivative, or the pharmaceutically acceptable salt, the hydrate, or the metabolite formed by the metabolism in any form thereof according to claim 1, wherein R5 is

### Claim 12 (depends on 10)

The use according to claim 10, wherein the indications associated with angiogenesis include malignant tumor diseases.

### Claim 13 (depends on 10)

A method for preventing and/or treating indications associated with angiogenesis in a subject, comprising:
administering to the subject an effective amount of the medicine according to claim 10.

### Claim 14 (depends on 13)

The method according to claim 13, wherein the indications associated with angiogenesis include malignant tumor diseases.