Acrylketone derivative of N-methyl lomefloxacin and preparation method and application of acrylketone derivative

A technology of methyllomefloxacin and acrylone, which is applied in the field of drug synthesis, can solve problems such as the uncertainty of the effect of the C-3 carboxyl group of fluoroquinolones, increase anti-tumor activity and anti-drug resistance, improve activity, and reduce toxic and side effects Effect

Active Publication Date: 2020-09-11
HENAN UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, it is uncertain whether the C-3 carboxyl group of fluoroquinolones can be replaced by different groups to obtain the effect

Method used

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  • Acrylketone derivative of N-methyl lomefloxacin and preparation method and application of acrylketone derivative
  • Acrylketone derivative of N-methyl lomefloxacin and preparation method and application of acrylketone derivative
  • Acrylketone derivative of N-methyl lomefloxacin and preparation method and application of acrylketone derivative

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] 1-Ethyl-6,8-difluoro-7-(3,4-dimethylpiperazin-1-yl)-3-cinnamoyl-quinoline-4(1 H )-ketone (I-1), its chemical structural formula is: , that is, Ar in formula I is phenyl.

[0032] The preparation method of compound (I-1) is as follows:

[0033] (1) Using N-methyllomefloxacin shown in formula II as raw material, reacting with carbonyldiimidazole (CDI) to prepare N-methyllomefloxacin imidazole amide compound shown in formula III, the specific preparation method is as follows :

[0034]

[0035] Take 1-ethyl-6,8-difluoro-7-(3,4-dimethylpiperazin-1-yl)-quinoline-4(1 H 22.0 g (60.0 mmol) of )-keto-3-carboxylic acid II was dissolved in 500 mL of anhydrous acetonitrile, 15.2 g (94.0 mmol) of carbonyldiimidazole was added, and the mixed reactant was stirred and refluxed in a water bath until the raw material II disappeared. Leave it at room temperature, collect the resulting solid by filtration, and recrystallize with acetone to obtain N-methyllomefloxacin imidazolamide ...

Embodiment 2

[0044] 1-Ethyl-6,8-difluoro-7-(3,4-dimethylpiperazin-1-yl)-3-(4-methoxycinnamoyl)-quinoline-4(1 H )-ketone (I-2), its chemical structural formula is:

[0045] That is, Ar in formula I is p-methoxyphenyl.

[0046] The preparation method of compound (I-2) is as follows:

[0047] (1) 1-ethyl-6,8-difluoro-7-(3,4-dimethylpiperazin-1-yl)-quinoline-4(1 H )-ketone-3-ethanone V is prepared referring to steps (1)-(3) of Implementation 1, replacing the solvent in step (1) with THF, N- The molar ratio of methyllomefloxacin to carbonyldiimidazole is 1:1.0;

[0048] (2) Take 1-ethyl-6,8-difluoro-7-(3,4-dimethylpiperazin-1-yl)-quinoline-4(1 H 1.1 g (3.0 mmol) of )-keto-3-ethanone V was dissolved in 20 mL of absolute ethanol, and 0.57 g (4.2 mmol) of 4-methoxybenzaldehyde and base catalyst piperidine (0.1 mL) were added. The mixed reactants were refluxed for 20 h, left at room temperature, and the resulting solid was collected by filtration and recrystallized from absolute ethanol to o...

Embodiment 3

[0050] 1-Ethyl-6,8-difluoro-7-(3,4-dimethylpiperazin-1-yl)-3-(3,4-dioxymethylenecinnamoyl)-quinoline-4 (1 H )-ketone (I-3), its chemical structural formula is:

[0051] , that is, Ar in formula I is 3,4-(dioxymethylene)phenyl.

[0052] The preparation method of compound (I-3) is as follows:

[0053] (1) 1-ethyl-6,8-difluoro-7-(3,4-dimethylpiperazin-1-yl)-quinoline-4(1 H )-ketone-3-ethanone V is prepared referring to steps (1)-(3) of Implementation 1, replacing the solvent in step (1) with dioxane, N- The molar ratio of methyllomefloxacin to carbonyldiimidazole is 1:2.0;

[0054] (2) Take 1-ethyl-6,8-difluoro-7-(3,4-dimethylpiperazin-1-yl)-quinoline-4(1 H )-keto-3-ethanone V1.1g (3.0 mmol) was dissolved in 20 mL of absolute ethanol, 0.53 g (3.5 mmol) of 3,4-dioxymethylene benzaldehyde and base catalyst piperidine (0.1 mL ). The mixed reactants were refluxed for 20 h, left at room temperature, and the resulting solid was collected by filtration and recrystallized from a...

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Abstract

The invention belongs to the field of drug synthesis, and relates to a derivative of N-methyl lomefloxacin, in particular to an acrylketone derivative of N-methyllomefloxacin and a preparation methodand application of the acrylketone derivative. The acrylketone derivative of N-methyllomefloxacin has the following structural general formula (I): in the formula, Ar is selected from any one of a benzene ring, a furan ring or a pyridine ring and a substituent group thereof. According to the acrylketone derivative of N-methyl lomefloxacin, a fluoroquinolinone skeleton and an acrylketone skeleton are effectively spliced, so that a novel fluoroquinolinone chalcone-like compound is constructed, the antitumor activity and the drug resistance of the novel compound are improved, the toxic and side effects on normal cells are reduced, and the fluoroquinolinone chalcone-like compound can be used as an antitumor active substance to develop antitumor drugs with brand new structures.

Description

technical field [0001] The invention belongs to the field of drug synthesis and relates to N- The derivative of methyllomefloxacin, in particular, refers to an acrylone derivative of N-methyllomefloxacin and its preparation method and application. Background technique [0002] N-methyllomefloxacin belongs to fluoroquinolones, and its antibacterial activity in vitro is similar to norfloxacin, slightly worse than ciprofloxacin, but its antibacterial activity in vivo includes E. Bacteria were significantly better than norfloxacin. The mechanism of action is the same as norfloxacin. At present, the drug is mainly used for genitourinary system infection and intestinal infection. As the lead of new drugs, based on the structure or mechanism of N-methyllomefloxacin, research and discovery of new drugs is an effective method for new drug innovation. [0003] The acrylone structure is not only the characteristic structure of natural active ingredients chalcones, but also the char...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D401/04A61P35/00A61P35/02
CPCA61P35/00A61P35/02C07D401/04
Inventor 曹玉辉黄帅崔红艳胡国强
Owner HENAN UNIVERSITY
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