# US 10,307,412 B2 · Quinoline derivative against non-small cell lung cancer

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- Number: US 10,307,412 B2
- Document ID: US10307412B2
- Status: Granted
- Kind: B2
- Application number: 15/533,873
- Filed: 2015-12-09
- Published: 2017-10-26
- Granted: 2019-06-04
- Earliest claimed: 2014-12-09
- Applicants: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
- Inventors: Xunqiang Wang; Yadong Miu; Min Zhou; Shanchun Wang; Ling Yang; Wei Shi
- Web page: https://patentgrep.com/patent/US10307412B2

## CPC

- A61K 31/4709: Non-condensed quinolines and containing further heterocyclic rings
- A61K 31/4035: Isoindoles, e.g. phthalimide
- A61P 35/00: Antineoplastic agents
- A61P 35/04: specific for metastasis
- C07D 401/12: linked by a chain containing hetero atoms as chain links
- A61K 9/0014: {Skin, i.e. galenical aspects of topical compositions (non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00)}
- A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)}
- A61K 9/0031: {Rectum, anus}
- A61K 9/0034: {Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants}
- A61K 9/006: {Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays}
- A61K 9/0073: {Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy; (nasal sprays A61K9/0043; inhalation of vapours of volatile or heated drugs, e.g. essential oils or nicotine, A61K9/007; devices A61M)}
- A61K 9/16: Agglomerates; Granulates; Microbeadlets {; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction (A61K9/20 takes precedence if the final form is a tablet; microspheres with drug-free outer coating, microcapsules A61K9/50; mixture of different granules, microcapsules, (coated) microparticles A61K9/5084; nanoparticles A61K9/51)}
- A61K 9/20: Pills, tablets, {discs, rods (A61K9/0004, A61K9/0007, A61K9/0056, A61K9/0065 take precedence; for reconstitution of a drink A61K9/0095)}
- A61K 9/4858: {Organic compounds}
- A61K 9/4866: {Organic macromolecular compounds}
- 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
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

The present application provides a quinoline derivative against non-small cell lung cancer. 1-[[[4-(4-fluoro-2-methyl)-1H-indol-5-yl)oxy-6-methoxyquinolin-7-yl]oxy]methyl]cyclopropylamine or a pharmaceutically acceptable salt thereof provided by the present application can be used for the treatment of non-small cell lung cancer, and relative to placebo, can significantly improve non-small cell lung cancer patients without progression of survival. 1-[[[4-(4-fluoro-2-methyl-1H-indol-5-yl)oxy-6-methoxyquinolin-7-yl]oxy]methyl]cyclopropylamine or a pharmaceutically acceptable salt thereof provided by the present application can be used for the treatment of lung adenocarcinoma, and relative to placebo, can significantly improve lung adenocarcinoma patients without progression of survival.

## Claims

### Claim 1

A method of treating advanced and/or metastatic non-small cell lung cancer, the method comprising:
orally administering to a human patient in need of treatment who has received a second-line or a higher-line therapy a therapeutically effective amount of compound I having the following structural formula or a pharmaceutically acceptable salt thereof,
wherein Compound I or the pharmaceutically acceptable salt thereof is administered at intervals and the ratio of the number of days in the dosing period to the withdrawal period is 2:0.5 to 2.

### Claim 2 (depends on 1)

The method according to claim 1, wherein the non-small cell lung cancer is EGFR mutant-negative non-small cell lung cancer.

### Claim 3 (depends on 1)

The method according to claim 1, wherein the non-small cell lung cancer is lung adenocarcinoma.

### Claim 4 (depends on 1)

The method according to claim 1, wherein the non-small cell lung cancer is EGFR mutant-negative lung adenocarcinoma.

### Claim 5 (depends on 1)

The method according to claim 1, wherein the said compound I or the pharmaceutically acceptable salt thereof is a hydrochloride of compound I.

### Claim 6 (depends on 1)

The method according to claim 1, wherein compound I or the pharmaceutically acceptable salt thereof is administered for 2 weeks and then suspended for 1 week.

### Claim 7 (depends on 6)

The method according to claim 6, wherein the daily dose of Compound I or the pharmaceutically acceptable salt is from 3 mg to 30 mg.

### Claim 8 (depends on 1)

The method according to claim 1, wherein compound I or the pharmaceutically acceptable salt thereof is administered once per day with an oral solid preparation.

### Claim 9 (depends on 1)

The method according to claim 1, wherein a dose of 8 mg, 10 mg, or 12 mg of compound I or the pharmaceutically acceptable salt thereof is administered once per day for 2 weeks and then suspended for 1 week.

### Claim 10

A method of treating advanced and/or metastatic non-small cell lung cancer, the method comprising:
orally administering to a human patient having non-small cell lung cancer who has received a second-line or a higher-line therapy a pharmaceutical composition comprising a therapeutically effective amount of a compound having the structural formula of Compound I and at least one pharmaceutically acceptable carrier,
wherein the pharmaceutical composition is administered at intervals, the ratio of the number of days in the dosing period to the withdrawal period is 2:0.5 to 2.

### Claim 11 (depends on 10)

The method according to claim 10, wherein non-small cell lung cancer is EGFR mutation negative non-small cell lung cancer.

### Claim 12 (depends on 10)

The method according to claim 10, wherein the pharmaceutical composition is a tablet, a capsule, a powder, a granule, or a dropping pill.

### Claim 13 (depends on 1)

The method according to claim 1, wherein compound I or the pharmaceutically acceptable salt thereof comprises a monohydrochloride salt of compound I.

### Claim 14 (depends on 1)

The method according to claim 1, wherein compound I or the pharmaceutically acceptable salt thereof comprises a dihydrochloride salt of compound I.

### Claim 15 (depends on 10)

The method according to claim 10, wherein the pharmaceutical composition is administered for 2 weeks and then suspended for 1 week.

### Claim 16 (depends on 10)

The method according to claim 10, wherein the pharmaceutical composition is administered for 2 weeks once per day and then suspended for 1 week.