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Quinoline derivatives and their preparation methods and applications

A quinoline and derivative technology, which can be used in drug combinations, pharmaceutical formulations, active ingredients of heterocyclic compounds, etc., and can solve the problems of drug resistance and low selectivity.

Active Publication Date: 2015-10-28
TIANJIN GREENPINE PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

For nearly a century, remarkable achievements have been made in the drug treatment of cancer. Dozens of anti-tumor drugs have been developed, which effectively prolong the life of patients or improve the quality of life of patients. However, most drugs are cytotoxic drugs, selective Not high and there is a problem of drug resistance

Method used

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  • Quinoline derivatives and their preparation methods and applications
  • Quinoline derivatives and their preparation methods and applications
  • Quinoline derivatives and their preparation methods and applications

Examples

Experimental program
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preparation example Construction

[0076] (1) Preparation of intermediates:

[0077] 6-Bromo-3-(chloro(phenyl)methyl)-2-methoxyquinoline

[0078] No.: M-01

[0079] Reference: Cai Zhiqiang, Sun Tiemin. Synthesis of 6-bromo-3-(chlorophenylmethyl)-2-methoxyquinoline. Synthetic Chemistry, 2009,17(5): 640~ 641.

Embodiment 1

[0081] 1-(4-((6-Bromo-2-methoxyquinolinyl-3-yl)(phenyl)methylamino)acetophenone Code: M-02)

[0082]

[0083] Experimental operation: Add 10.0 g (0.028mol) 6-bromo-3-(chloro(phenyl)methyl)-2-methoxyquinoline (code: M-01), 3.74 g (0.028mol) of p-aminoacetophenone, 3.82 g (0.028mol) of potassium carbonate, 0.232 g (0.0014mol) of potassium iodide and 100 mL of acetonitrile, heated to reflux for 5 hours. Evaporate the solvent to dryness, add water, extract with (50 mL×3) dichloromethane, combine the organic phases, dry over anhydrous magnesium sulfate, filter, evaporate the solvent to dryness, and purify by column chromatography to obtain a white solid. 1-(4-((6-bromo-2-methoxyquinolinyl-3-yl)(phenyl)methylamino)acetophenone (1-(4-((6-bromo-2-methoxyquinolin -3-yl)(phenyl)methylamino)phenyl)ethan-one, number: M-02) 4.75 g, yield 37.2%.

Embodiment 2

[0085] N-(4-acetylphenyl)-N-((6-bromo-2methoxyquinolinyl-3-yl)(phenyl)methyl)-2-chloroacetamide, Code: M-03

[0086] (N-(4-acetylphenyl)-N-((6-bromo-2-methoxyquinolin-3-yl)(phenyl)methyl)-2-chloroacetamide, number: M-03)

[0087]

[0088] Reagents and reaction conditions: Et 3 N, CH 2 Cl 2 , room temperature

[0089] Experimental operation: Add 1.38 g (0.003mol) 1-(4-((6-bromo-2-methoxyquinolinyl-3-yl)(phenyl)methylamino)phenethyl Ketone (1-(4-((6-bromo-2-methoxyquinolin-3-yl)(phenyl)methylamino)phenyl)ethanone, code: M-02) and dichloromethane 30 mL, stirred to dissolve, add 4 mL three Ethylamine, add 3 mL of chloroacetyl chloride dropwise, a large amount of white smoke appears, gradually becomes turbid, stir at room temperature for 3 hours. Add a small amount of ammonia water to adjust pH=8, extract with (30 mL×2) dichloromethane, combine organic phases, Dry over anhydrous magnesium sulfate, filter, evaporate the solvent to dryness, and purify by column chromatogr...

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Abstract

The invention relates to novel substituted quinoline derivatives shown as the general formula I and medicinal acid addition salts of the novel substituted quinoline derivatives. The compounds provided by the invention are specially defined as the specification, wherein R1 and R2 are respectively independent methyl, ethyl or benzyl, or R1 and R2 and N connected with R1 and R2 can form 4-methyl-piperidyl or morpholinyl, and n=1 or 2. The invention also relates to preparation methods of the compounds provided by the invention. Pharmacological activity screening tests show that the compounds have remarkable hyperplasia preventing effects for cancer cells in vivo and in vitro, and parts of compounds have remarkable tumor suppression activity, such as lung cancer, liver cancer, breast cancer and pancreatic cancer. Particularly, the tumor inhibiting rate of the pancreatic cancer PANC (Pancreatic Cancer Cell)-1 is up to 46.7%.

Description

technical field [0001] The invention belongs to the technical field of medicinal chemistry, relates to quinoline derivatives and a preparation method thereof, and also relates to the application of the derivatives in the preparation of drugs for treating tumors. Background technique [0002] Cancer is a serious threat to human life and health, and it is one of the leading causes of death for human beings. It is extremely difficult to treat. Since the late 20th century, the incidence of cancer has been on the rise, and the patients are younger. According to the statistics of the World Health Organization, about 5 million patients die from cancer every year in the world. It is predicted that there will be 20 million new cancer cases by 2020, of which the death toll will reach 12 million. For nearly a century, remarkable achievements have been made in the drug treatment of cancer. Dozens of anti-tumor drugs have been developed, which effectively prolong the life of patients or...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D215/227C07D401/12A61K31/5377A61K31/4709A61K31/47A61P35/00
Inventor 沈载宽郑林海孙铁民
Owner TIANJIN GREENPINE PHARMA