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Levofloxacin aldolase thiosemicarbazide derivative and preparation method and application thereof

A technology of levofloxacin aldehyde amino reduction and star aldehyde amino reduction, which is applied in the field of new drug discovery and innovative drug synthesis

Inactive Publication Date: 2017-06-06
HENAN UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, most of the aldehydes or ketones used to construct thiosemicarbazone molecules are common benzenes or heterocyclic aromatic aldehydes and ketones, while quinoline aldehydes, especially thiosemicarbazones formed by fluoroquinolinone aldehydes, are currently Not yet reported

Method used

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  • Levofloxacin aldolase thiosemicarbazide derivative and preparation method and application thereof
  • Levofloxacin aldolase thiosemicarbazide derivative and preparation method and application thereof
  • Levofloxacin aldolase thiosemicarbazide derivative and preparation method and application thereof

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Experimental program
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Effect test

Embodiment 1

[0046] (S)-6-fluoro-7-(4-methyl-piperazin-1-yl)-1,8-(2,1-oxypropyl)-quinoline-4(1H)-one-3- Aldehyde thiosemicarbazone (I-1), its chemical structure is:

[0047]

[0048] That is, R in formula I is a H atom.

[0049] The preparation method of the compound is as follows: take the crude levofloxacin aldehyde represented by formula (IV) (1.0g) and dissolve it in absolute ethanol (20ml), add thiosemicarbazide (0.5g, 5.5mmol), reflux and react for 12 hours, while hot After filtration, the solid was washed twice with ethanol, washed twice with distilled water, dried, and recrystallized with DMF-ethanol (V:V=5:3) mixed solvent to obtain light yellow crystals of formula (I-1) to obtain the product 0.48g, mp231~233℃. 1 H NMR(400MHz, DMSO-d 6 )δ: 11.43(s,1H,CH=N),8.76(s,1H,2-H), 8.44(s,1H,NH),8.36(s,1H,NH 2 ),8.33(s,1H,NH 2 ),7.47(d,1H,5-H), 4.62~4.34(m,3H, OCH 2 CHN), 3.24(t,4H, piperazine-H), 2.55(t,4H, piperazine-H), 2.26(s,3H, N-CH 3 ), 1.45(d,3H,CH 3 ); MS(m / z): Calcd.for C 19 H 23 FN 6...

Embodiment 2

[0051] (S)-6-fluoro-7-(4-methyl-piperazin-1-yl)-1,8-(2,1-oxypropyl)-quinoline-4(1H)-one-3- Aldehyde 4-methylthiosemicarbazide (I-2), its chemical structure is:

[0052]

[0053] That is, R in formula I is a methyl group.

[0054] The preparation method of this compound is as follows: Take the levofloxacin aldehyde hydrazinodithioformate methyl ester (1.0g, 2.23mmol) represented by formula (VI) and dissolve it in anhydrous n-butanol (20ml), add methylamine ( 0.68g, 22.0mmol), the mixed reactants were refluxed and reacted for 12 hours, filtered while hot, and the solids were washed twice with ethanol, washed with distilled water twice, dried, and re-weighted with DMF-ethanol (V:V=1:5) mixed solvent Crystallize to obtain 0.33 g of the product of formula (I-2) as yellow crystals, mp 210-212°C. 1 H NMR(400MHz, DMSO-d 6 )δ: 11.46(s,1H,CH=N),8.77(s,1H,2-H), 8.36(s,1H,NH),8.35(s,1H,NH),7.46(d,1H,5 -H), 4.57~4.32(m,3H, OCH 2 CHN), 3.24(t,4H, piperazine-H), 3.12(d,3H,NH-CH 3 ), 2.47(t,4H, ...

Embodiment 3

[0056] (S)-6-fluoro-7-(4-methyl-piperazin-1-yl)-1,8-(2,1-oxypropyl)-quinoline-4(1H)-one-3- Aldehyde 4-ethylthiosemicarbazide (I-3), its chemical structure is:

[0057]

[0058] That is, R in formula I is ethyl.

[0059] The preparation method of the compound is as follows: take the levofloxacin aldehyde hydrazinodithioformate methyl ester (1.0g, 2.23mmol) represented by formula (VI) and dissolve it in anhydrous n-butanol (20ml), add ethylamine ( 0.90g, 20.0mmol), the mixed reactants were refluxed and reacted for 12 hours, filtered while hot, and the solids were washed twice with ethanol, washed with distilled water twice, dried, and weighed with DMF-ethanol (V:V=1:5) mixed solvent After crystallization, 0.48g of yellow crystalline product of formula (I-3) was obtained, mp204~206℃. 1 H NMR(400MHz, DMSO-d 6 )δ: 11.42(s,1H,CH=N),8.77(s,1H,2-H), 8.43(d,1H,NH),8.33(s,1H,NH),7.42(d,1H,5 -H), 4.57~4.33(m,3H, OCH 2 CHN), 3.58(m,2H,CH 2 ), 3.24(t,4H, piperazine-H), 2.46(t,4H, piperazine-H...

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Abstract

The invention discloses levofloxacin aldolase thiosemicarbazide derivative and a preparation method and application thereof. A chemical structure general formula shown in the formula is adopted, wherein R is hydrogen atom and alkyl or cyclopropyl with 1-5 carbon atoms. According to the levofloxacin aldolase thiosemicarbazide derivative, splicing of advantageous pharmacophores of a chiral fluoroquinolone skeleton, schiff base imine and thiourea is achieved, so that the anti-tumor activity of a novel compound is improved, the toxic or side effect on a normal cell is reduced, and the levofloxacin aldolase thiosemicarbazide derivative can be used for developing an anti-tumor drug of a bran-new structure as an anti-tumor active material.

Description

Technical field [0001] The invention belongs to the technical field of new drug discovery and innovative drug synthesis, and specifically relates to a levofloxacin aldehyde thiosemicarbazone derivative, and also relates to a preparation method of the levofloxacin aldehyde thiosemicarbazone derivative, and its application in antitumor drugs In the application. Background technique [0002] New drug innovation originated from the discovery of the leader, and it is the most economical and effective strategy to construct the leader molecule based on the splicing of the backbone of the dominant pharmacophore. Thiosemicarbazone derivatives constructed from aldehydes or ketones and thiosemicarbazides have attracted much attention because of their easy production of complexes or chelation with macromolecules or metal ions. However, the aldehydes or ketones that construct thiosemicarbazone molecules are mostly common benzene or heterocyclic aromatic aldehydes and ketones, while quinolina...

Claims

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Application Information

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IPC IPC(8): C07D498/06A61P35/00A61P35/02
CPCC07D498/06
Inventor 赵芬琴张维瑞杨彤汪学猛沈睿智王娜胡国强
Owner HENAN UNIVERSITY
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