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Isorcryptolepine analogue prepared by taking ofloxacin as raw material, and preparation method and application thereof

A technology of isofloxacin and ofloxacin, applied in the direction of organic chemistry, antibacterial drugs, etc., can solve the problems of difficult source, poor water solubility, low bioavailability, etc. The effect of inhibiting the growth activity of Mycobacterium tuberculosis, increasing penetration, and improving water solubility

Inactive Publication Date: 2022-02-01
ZHENGZHOU UNIV OF IND TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] However, due to the difficulty in the source of vine alkaloids, coupled with poor water solubility, resulting in low bioavailability and other defects, the clinical application is limited.

Method used

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  • Isorcryptolepine analogue prepared by taking ofloxacin as raw material, and preparation method and application thereof
  • Isorcryptolepine analogue prepared by taking ofloxacin as raw material, and preparation method and application thereof
  • Isorcryptolepine analogue prepared by taking ofloxacin as raw material, and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036] 2-Fluoro-3-(4-methylpiperazin-1-yl)-4,5-isopropoxy-5H-indolo[3,2-c]quinoline (I-1), its chemical The structural formula is:

[0037]

[0038] That is, R in formula I is an H atom.

[0039] The preparation method of the compound (I-1) is: take 1,8-isopropoxy-6-fluoro-7-(4-methylpiperazin-1-yl)-quinolin-4(1H)-one 1.0g (3.0mmol) of III was dissolved in 15mL of absolute ethanol, 0.50g (4.6mmol) of phenylhydrazine was added, and the reaction was stirred at room temperature for 12h (the raw material III disappeared as observed by TLC), and a large amount of precipitate was formed. Concentrated hydrochloric acid (0.50 mL) was added as a cyclization catalyst, and the mixed reactants were refluxed for 10 h and left overnight (12 h, the same below). Collect the resulting solid by filtration, dissolve the solid with 50 mL of deionized water, add an appropriate amount of activated carbon, and reflux for 1 h for decolorization. Filtrate hot, and adjust the pH of the filtrate t...

Embodiment 2

[0041] 2-fluoro-8-methoxy-3-(4-methylpiperazin-1-yl)-4,5-isopropoxy-5H-indolo[3,2-c]quinoline (I -2), its chemical structural formula is:

[0042]

[0043] That is, R in formula I is methoxy.

[0044] The preparation method of this compound (I-2) is: take 1,8-isopropoxy-6-fluoro-7-(4-methylpiperazin-1-yl)-quinolin-4(1H)-one Dissolve 1.0g (3.0mmol) of III in 15mL of absolute ethanol, add 0.62g (4.5mmol) of p-methoxyphenylhydrazine, stir and react at room temperature for 16h (the disappearance of raw material III was observed by TLC), and an obvious precipitate is formed. Concentrated hydrochloric acid (0.50 mL) was added, and the mixed reactants were refluxed for 12 h and left overnight. Collect the resulting solid by filtration, dissolve the solid with 50 mL of deionized water, add an appropriate amount of activated carbon, and reflux for 1 h for decolorization. Filtrate hot, and adjust the pH of the filtrate to ≈10.0 with ammonia water. The resulting solid was collecte...

Embodiment 3

[0046] 2-fluoro-9-methoxy-3-(4-methylpiperazin-1-yl)-4,5-isopropoxy-5H-indolo[3,2-c]quinoline (I -3), its chemical structural formula is:

[0047]

[0048] That is, R in formula I is methoxy.

[0049] The preparation method of the compound (I-3) is: take 1,8-isopropoxy-6-fluoro-7-(4-methylpiperazin-1-yl)-quinolin-4(1H)-one 1.0 g (3.0 mmol) of III was dissolved in 15 mL of absolute ethanol, 0.83 g (6.0 mmol) of m-methoxyphenylhydrazine was added, and the reaction was stirred at room temperature for 20 h (the disappearance of raw material III was observed by TLC), and an obvious precipitate was formed. Concentrated hydrochloric acid (0.50 mL) was added, and the mixed reactants were refluxed for 15 h and left overnight. Collect the resulting solid by filtration, dissolve the solid with 50 mL of deionized water, add an appropriate amount of activated carbon, and reflux for 1 h for decolorization. Filtrate hot, and adjust the pH of the filtrate to ≈10.0 with ammonia water. T...

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PUM

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Abstract

The invention discloses an isocryptolepine analogue, and a preparation method and application thereof. The chemical structure of the isocryptolepine analogue is shown as a formula I. The substituent group R in the formula I can be independently -H, -OCH3, -F, -Cl or -SO2NH2. According to the isocryptolepine analogue disclosed by the invention, ofloxacin is taken as a raw material, so that effective chemical construction from a fluoroquinolone structure to an indoloquinoline skeleton is realized, and a new way for structural modification of isocryptolepine is expanded, so that the anti-tubercle bacillus activity and the anti-drug resistance of the compound are improved, the toxicity to normal cells is reduced, and the isocryptolepine analogue can be further developed as an antituberculous drug with a brand new structure.

Description

technical field [0001] The invention belongs to the technical field of medicinal chemistry related to organic synthesis and research and development of new drugs, and specifically relates to an isoalvanine analogue, and also relates to a method for preparing an isoalvanine analogue using ofloxacin as a raw material , and its application in the preparation of anti-tuberculosis drugs. Background technique [0002] Tuberculosis is a chronic infectious disease with a high incidence rate caused by Mycobacterium tuberculosis. Due to the lack of effective treatment drugs, it has become an urgent public health and social problem facing the world. At the same time, coupled with the fact that Mycobacterium tuberculosis is prone to drug resistance to existing drugs, especially the generation of multidrug resistance, it poses new challenges to the development of anti-tuberculosis drugs. There is not yet a new compound for the treatment of tuberculosis. Therefore, the research and deve...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D498/16A61P31/06
CPCC07D498/16A61P31/06
Inventor 刘启玲王桁杰郑宝玉付培蕾李金鸽
Owner ZHENGZHOU UNIV OF IND TECH
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