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Quinoline derivatives for the treatment of triple negative breast cancer

A triple-negative breast cancer, post-treatment technology, applied in the field of medicine, can solve the problem of lack of necessity and urgency of treatment options

Active Publication Date: 2022-07-08
CHIA TAI TIANQING PHARMA GRP CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The lack of treatment options suggests the need and urgency to develop effective therapies against TNBC

Method used

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  • Quinoline derivatives for the treatment of triple negative breast cancer
  • Quinoline derivatives for the treatment of triple negative breast cancer
  • Quinoline derivatives for the treatment of triple negative breast cancer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 11

[0087] Example 1 1-[[[4-(4-Fluoro-2-methyl-1H-indol-5-yl)oxy-6-methoxyquinolin-7-yl]oxy]methyl] Cyclopropylamine dihydrochloride

[0088]

[0089] 1-[[[4-(4-Fluoro-2-methyl-1H-indol-5-yl)oxy-6-methoxyquinolin-7-yl was prepared with reference to the method of Example 24 in WO2008112407 ]oxy]methyl]cyclopropylamine, and then according to the preparation method of "Example in salt form" in the specification of WO2008112407, the title compound was prepared.

[0090] Or prepared by referring to the method disclosed in Chinese patent application CN102344438A.

Embodiment 21

[0091] Example 2 1-[[[4-(4-Fluoro-2-methyl-1H-indol-5-yl)oxy-6-methoxyquinolin-7-yl]oxy]methyl] Preparation of capsules of cyclopropylamine dihydrochloride (dihydrochloride of compound I)

[0092]

[0093]

[0094] The dihydrochloride of compound I is pulverized, crossed with 80 mesh sieves; then mixed with mannitol and hydroxypropyl cellulose; then added the microcrystalline cellulose of the recipe quantity, mixed homogeneously, crossed the 0.8mm sieve; finally added the recipe quantity of magnesium stearate, mix well and fill the capsules.

[0095] For capsules with other contents of the dihydrochloride of compound I, it can be prepared with reference to the same proportion and prescription above.

Embodiment 3

[0096] Example 3 Clinical trial

[0097] A clinical trial of Compound I dihydrochloride capsules was conducted in female patients ≥18 years of age with advanced or metastatic triple-negative breast cancer (ER-negative, PR-negative, HER2-negative) with measurable disease (according to RECIST 1.1), patients Received or not previously received chemotherapy, compound I dihydrochloride capsules alone or in combination with chemotherapy, administered at 12 mg, once a day, according to the regimen of continuous administration for two weeks and one week off, that is, every 3 One week is a medication cycle. Evaluation indicators include efficacy indicators: progression-free survival (PFS), objective response rate (ORR), duration of response (DOR), stable disease (SD) rate, clinical benefit rate (CBR), overall survival (OS), etc. ; Safety indicators: incidence and severity of adverse reactions; quality of life, etc.

[0098] Clinical trial results:

[0099] The dihydrochloride salt o...

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Abstract

The present invention provides a quinoline derivative for treating triple-negative breast cancer and its use in preparing a pharmaceutical composition for tumor treatment. Specifically, the present invention relates to quinoline derivatives 1-[[[4-(4-fluoro-2-methyl-1H-indol-5-yl)oxy-6-methoxyquinoline-7- Use of oxy]oxy]methyl]cyclopropylamine in the treatment of triple negative breast cancer, (I).

Description

technical field [0001] The invention belongs to the field of medicine, and relates to the use of quinoline derivatives in the preparation of pharmaceutical compositions for tumor treatment. In particular, the present invention relates to the use of quinoline derivatives in the treatment of triple negative breast cancer. Background technique [0002] Triple-negative breast cancer (TNBC) refers to estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (human epidermal growth factor receptor). -2, HER2) expression was negative for breast cancer. TNBC accounts for approximately 15-20% of the 1.7 million new breast cancers diagnosed worldwide each year. TNBC has unique pathological and clinical features, it has an aggressive phenotype and high metastasis rate, and the prognosis is poorer than other types. The 5-year survival rate for TNBC is 70%, while the 5-year survival rate for other types of breast cancer is about 80%. [0003] TNB...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/4709A61P35/00
CPCA61P35/00A61K31/4709A61K31/675A61K31/7068A61K31/337A61K31/704A61K33/243A61K9/4858A61K9/4866A61K9/0053
Inventor 田心吕鹏杨玲王祥建张喜全王善春王训强江海
Owner CHIA TAI TIANQING PHARMA GRP CO LTD
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