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Acrylone derivative of n-methyllomefloxacin and its preparation method and application

A technology of methyllomefloxacin and methyllomefloxacin imidazole amide, 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, reduce Toxic effects

Active Publication Date: 2021-11-19
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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  • Acrylone derivative of n-methyllomefloxacin and its preparation method and application
  • Acrylone derivative of n-methyllomefloxacin and its preparation method and application
  • Acrylone derivative of n-methyllomefloxacin and its preparation method and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032] 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.

[0033] The preparation method of compound (I-1) is as follows:

[0034] (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 :

[0035]

[0036] 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

[0045] 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:

[0046] That is, Ar in formula I is p-methoxyphenyl.

[0047] The preparation method of compound (I-2) is as follows:

[0048] (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;

[0049] (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

[0051] 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:

[0052] , that is, Ar in formula I is 3,4-(dioxymethylene)phenyl.

[0053] The preparation method of compound (I-3) is as follows:

[0054] (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;

[0055] (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 ...

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Abstract

The invention belongs to the field of drug synthesis and relates to N‑ A derivative of methyllomefloxacin, in particular a propenone derivative of N-methyllomefloxacin and a preparation method and application thereof. N‑ The acrylone derivative of methyllomefloxacin has the following general structural formula (I): in the formula, Ar is any one selected from a benzene ring, a furan ring or a pyridine ring and substituents thereof. of the present invention N‑ The propenone derivative of methyllomefloxacin realizes the effective splicing of the fluoroquinolone skeleton and the propenone skeleton, and then constructs a new fluoroquinolone "chalcone-like" compound, thereby increasing the antitumor activity of the new compound And anti-drug resistance, and reduce the toxic and side effects on normal cells, it can be used as an anti-tumor active substance to develop anti-tumor drugs with a new structure.

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 Patents(China)
IPC IPC(8): C07D401/04A61P35/00A61P35/02
CPCA61P35/00A61P35/02C07D401/04
Inventor 曹玉辉李佳桓黄帅崔红艳胡国强
Owner HENAN UNIVERSITY