Fleroxacin aldehyde acetal 4-aryl thiosemicarbazide derivatives and its preparation method and application

A technology of arylamino and fleroxacin, which is applied in drug combination, organic chemistry, antineoplastic drugs, etc.

Inactive Publication Date: 2019-05-31
ZHENGZHOU UNIV OF IND TECH
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  • Abstract
  • Description
  • Claims
  • Application Information

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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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  • Fleroxacin aldehyde acetal 4-aryl thiosemicarbazide derivatives and its preparation method and application
  • Fleroxacin aldehyde acetal 4-aryl thiosemicarbazide derivatives and its preparation method and application
  • Fleroxacin aldehyde acetal 4-aryl thiosemicarbazide derivatives and its preparation method and application

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Experimental program
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Embodiment 1

[0032] 1-(2-fluoroethyl)-6,8-difluoro-7-(4-methyl-piperazin-1-yl)-quinolin-4(1H)-one-3-aldehyde 4-benzeneacetal Thiosemicarbazide (I-1), its chemical structural formula is:

[0033]

[0034] That is, the Ar substituent in formula (I) is a benzene ring.

[0035] The preparation method of this compound is: the fleroxacin C-3 aldehyde crude product (1.0g) shown in formula (IV) is dissolved in dehydrated alcohol (30 milliliters), adds the 4-phenylthiosemicarbazide shown in formula (VIII) (0.6g, 3.6mmol), reflux reaction for 10 hours, filtered while hot, washed with ethanol twice, the solid was washed twice with distilled water, dried, and recrystallized with a mixed solvent of DMF-ethanol (V:V=5:3), The light yellow crystal formula (I-1) was obtained, and 0.68 g of the product was obtained, m.p.246-248°C. 1 H NMR (400MHz, DMSO-d 6 ): 11.82(s, 1H, CH=N), 10.05(s, 1H, NH), 8.97(s, 1H, 2-H), 8.46(s, 1H, NH), 7.96~7.48(m, 6H, Ph-H and 5-H),4.87(t,2H,FCH 2 ),4.68(t,2H,NCH 2 ),...

Embodiment 2

[0037] 1-(2-fluoroethyl)-6,8-difluoro-7-(4-methyl-piperazin-1-yl)-quinolin-4(1H)-one-3-aldehyde acetal 4-( 4-methylphenyl) thiosemicarbazide (I-2), its chemical structural formula is:

[0038]

[0039] That is, Ar in formula (I) is 4-methylphenyl.

[0040] The preparation method of this compound is: the fleroxacin C-3 aldehyde crude product (1.0g) shown in formula (IV) is dissolved in dehydrated alcohol (30 milliliters), adds the 4-(4-methyl aldehyde shown in formula (VIII) Phenyl)thiosemicarbazide (0.6g, 3.3mmol), reflux reaction for 12 hours, filtered while hot, the solid was washed twice with ethanol and distilled water twice, dried, and washed with DMF-ethanol (V:V=5:3 ) mixed solvent for recrystallization to obtain light yellow crystals of formula (I-2), 0.66 g of the product, m.p.235-237°C. 1 H NMR (400MHz, DMSO-d 6 ): 11.78(s, 1H, CH=N), 9.96(s, 1H, NH), 8.95(s, 1H, 2-H), 8.46(s, 1H, NH), 7.83~7.46(m, 5H, Ph-H and 5-H),4.86(t,2H,FCH 2 ),4.68(t,2H,NCH 2 ), 3.35 ...

Embodiment 3

[0042] 1-(2-fluoroethyl)-6,8-difluoro-7-(4-methyl-piperazin-1-yl)-quinolin-4(1H)-one-3-aldehyde acetal 4-( 4-methoxyphenyl) thiosemicarbazide (I-3), its chemical structural formula is:

[0043]

[0044] That is, Ar in formula (I) is 4-methoxyphenyl.

[0045] The preparation method of this compound is: the fleroxacin C-3 aldehyde crude product (1.0g) shown in formula (IV) is dissolved in dehydrated alcohol (30 milliliters), adds the 4-(4-methoxy compound shown in formula (VIII) phenyl) thiosemicarbazide (0.7g, 3.6mmol), reflux reaction for 8 hours, filtered while hot, the solid was washed twice with ethanol, washed twice with distilled water, dried, and washed with DMF-ethanol (V:V=5: 3) Recrystallization from the mixed solvent to obtain the pale yellow crystal formula (I-3), 0.76 g of the product, m.p.>250°C. 1 H NMR (400MHz, DMSO-d 6 ): 11.83(s, 1H, CH=N), 10.12(s, 1H, NH), 9.15(s, 1H, 2-H), 8.50(s, 1H, NH), 8.15~7.52(m, 5H, Ph-H and 5-H),4.88(t,2H,FCH 2 ),4.68(t,2H,N...

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Abstract

The invention discloses a fleroxacinaldehyde-4-aryl thiosemicarbazide derivative, as well as a preparation method and application thereof. The following chemical structural formula I is adopted: the formula is shown in the description, where a substituent Ar is a benzene ring or a substituted benzene ring or a pyridine ring or a furan ring or a thiophene ring. According to the fleroxacinaldehyde-4-aryl thiosemicarbazide derivative, three advantageous pharmacophores, i.e. a polyfluoroquinolone framework, Schiff base imine and thiourea, are mixed, thereby improving the anti-tumor activity of a new compound and reducing toxic or side effects on normal cells; the fleroxacinaldehyde-4-aryl thiosemicarbazide derivative can be used for developing an anti-tumor medicament of a new structure as an anti-tumor active substance.

Description

technical field [0001] The invention belongs to the technical field of new drug discovery and innovative drug synthesis, and specifically relates to a 4-aryl thiosemicarbazide derivative of fleroxacin aldehyde, and also relates to a 4-aryl thiosemicarbazide derivative of fleroxacin aldehyde The preparation method of and its application in antineoplastic drugs. Background technique [0002] The innovation of new drugs originates from the discovery of leads, and the construction of lead molecules based on the combination of dominant pharmacophore skeletons is the most economical and effective strategy. The thiosemicarbazone derivatives constructed from aldehydes or ketones and thiosemicarbazides have attracted much attention because they are easy to form complexes or chelate with macromolecules or metal ions, and exhibit a wide range of pharmacological activities. However, most of the aldehydes or ketones used to construct thiosemicarbazone molecules are common benzenes or he...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D215/38C07D401/12C07D405/12C07D409/12A61P35/00A61P35/02
CPCC07D215/38C07D401/12C07D405/12C07D409/12
Inventor 李阳杰张杨李星蔡元元胡国强
Owner ZHENGZHOU UNIV OF IND TECH
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