Eureka AIR delivers breakthrough ideas for toughest innovation challenges, trusted by R&D personnel around the world.

A kind of 3,3'-methylene-bisfluoroquinolone derivative of chiral oxazinoquinoline ring and its preparation method and application

A technology of bisfluoroquinolone and quinoline ring, applied in the field of drug synthesis

Inactive Publication Date: 2016-11-23
HENAN UNIVERSITY
View PDF2 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although there are many ways to discover new drugs, the structural modification of existing drugs is still the most successful and economical strategy for new drug development

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • A kind of 3,3'-methylene-bisfluoroquinolone derivative of chiral oxazinoquinoline ring and its preparation method and application
  • A kind of 3,3'-methylene-bisfluoroquinolone derivative of chiral oxazinoquinoline ring and its preparation method and application
  • A kind of 3,3'-methylene-bisfluoroquinolone derivative of chiral oxazinoquinoline ring and its preparation method and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035] (S)-6-fluoro-7-(4-methyl-piperazin-1-yl)-1,8-(3,1-oxopropyl)-3-[1-ethyl-6-fluoro- 7-piperazin-1-yl-2,3-dihydro-quinolin-4(1H)-one-3-ylidenemethyl]-quinolin-4(1H)-one (I-1), its chemical The structural formula is:

[0036]

[0037] That is, R in formula I is an ethyl group, and R 1 and R 2 is a hydrogen atom, and X is a hydrocarbon group.

[0038] The preparation method of the compound is: take 6-fluoro-7-(4-methyl-piperazin-1-yl)-1,8-(3,1-oxopropyl)-quinoline-4(1H)- Ketone (VI) 0.55g (1.6mmol) and 1-ethyl-6-fluoro-7-piperazin-1-yl-2,3-dihydro-quinolin-4(1H)-one (III-1) 0.44g (1.6mmol) was dissolved in 20mL of absolute ethanol, 0.2mL of piperidine was added dropwise, and the reaction was refluxed for 24h. After standing for 12 hours, the resulting solid was collected by filtration and recrystallized from DMF-ethanol (V:V=3:1) to obtain a light yellow crystal (I-1), with a yield of 82%, m.p.228-232°C. 1 H NMR (400MHz, DMSO-d 6 )δ: 7.91~7.88(brs,2H,2-H,3-CH=),7.7...

Embodiment 2

[0040] (S)-6-fluoro-7-(4-methyl-piperazin-1-yl)-1,8-(3,1-oxopropyl)-3-[1-ethyl-6-fluoro- 7-(4-methylpiperazin-1-yl)-2,3-dihydro-quinolin-4(1H)-one-3-ylidenemethyl]-quinolin-4(1H)-one (I -2), its chemical structural formula is:

[0041]

[0042] That is, R in formula I is an ethyl group, and R 1 is methyl, R 2 is a hydrogen atom, and X is CH.

[0043]The preparation method of the compound is: take 6-fluoro-7-(4-methyl-piperazin-1-yl)-1,8-(3,1-oxopropyl)-quinoline-4(1H)- Ketone (VI) 0.55g (1.6mmol) and 1-ethyl-6-fluoro-7-(4-methylpiperazin-1-yl)-2,3-dihydro-quinoline-4(1H)- Ketone (III-2) 0.50g (1.7mmol) was dissolved in 20mL absolute ethanol, triethylamine 0.2mL was added dropwise, and the reaction was refluxed for 20h. After standing for 12 hours, the resulting solid was collected by filtration and recrystallized with DMF-ethanol (V:V=3:1) to obtain a light yellow crystal (I-2), with a yield of 85%, m.p.225-227°C. 1 H NMR (400MHz, DMSO-d 6 )δ: 7.90~7.87(brs,2H,2-H,3-...

Embodiment 3

[0045] (S)-6-fluoro-7-(4-methyl-piperazin-1-yl)-1,8-(3,1-oxopropyl)-3-[1-cyclopropyl-6-fluoro -7-piperazin-1-yl-2,3-dihydro-quinolin-4(1H)-one-3-ylidenemethyl]-quinolin-4(1H)-one (I-3), which The chemical structural formula is:

[0046]

[0047] That is, R in formula I is cyclopropyl, R 1 and R 2 is a hydrogen atom, and X is a hydrocarbon group.

[0048] The preparation method of the compound is: take 6-fluoro-7-(4-methyl-piperazin-1-yl)-1,8-(3,1-oxopropyl)-quinoline-4(1H)- Ketone (VI) 0.55g (1.6mmol) and 1-cyclopropyl-6-fluoro-7-piperazin-1-yl-2,3-dihydro-quinolin-4(1H)-one (III-3 ) 0.52g (1.8mmol) was dissolved in 20mL absolute ethanol, piperidine 0.2mL was added dropwise, and the reaction was refluxed for 22h. After standing for 24 hours, the resulting solid was collected by filtration and recrystallized from DMF-ethanol (V:V=5:1) to obtain a light yellow crystal (I-3), with a yield of 86%, m.p.232-234°C. 1 H NMR (400MHz, DMSO-d 6 )δ: 7.92~7.88(brs,2H,2-H,3-CH=),7...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention discloses a 3,3'-methene-difluoroquinolone derivative of a chiral oxazine quinoline ring as well as a preparation method and application of the 3,3'-methene-difluoroquinolone derivative. The 3,3'-methene-difluoroquinolone derivative has a chemical general structural formula I shown in the specification, wherein R represents cyclopropyl or ethyl or fluoroethyl; R1 represents a hydrogen atom or methyl or ethyl; R2 represents a hydrogen atom or methyl; X represents a nitrogen atom or a hydrocarbon (CH) group or a fluoro-substituted carbon atom (F-C) or a methoxyl-substituted carbon atom (CH3O-C). The 3,3'-methene-difluoroquinolone derivative of the chiral oxazine quinoline ring, disclosed by the invention, can be used for realizing the superposition of a difluoroquinolone framework and alpha, beta-unsaturated ketone pharmacophores, so that the antitumor activity of a new compound is improved, the toxic and side effects on normal cells can be reduced, and the 3,3'-methene-difluoroquinolone derivative can be used as an antitumor active substance for developing an antitumor drug of a totally new structure.

Description

technical field [0001] The invention belongs to the technical field of drug synthesis, and specifically relates to a 3,3′-methylene-bisfluoroquinolone derivative compound of a chiral oxazinoquinoline ring, and also relates to a 3, A preparation method of 3'-methylene-bisfluoroquinolone derivative and its application in antineoplastic drugs. Background technique [0002] Tumor is one of the biggest diseases that threaten human life and health. Due to the high toxicity of current anti-tumor drugs and poor tolerance of patients, the cure rate of tumor diseases is low. Therefore, it is increasingly urgent to develop antitumor drugs with new structures. Although there are many ways to discover new drugs, the structural modification of existing drugs is still the most successful and economical strategy for new drug development. Based on the similarity in sequence and function between the target enzyme of antibacterial fluoroquinolones—topoisomerase and the corresponding topoiso...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Patents(China)
IPC IPC(8): C07D498/06C07D519/00A61K31/5383A61P35/00
CPCC07D498/06C07D519/00
Inventor 闫强胡海廷吴书敏倪礼礼李涛冯焱飞高留州谢玉锁胡国强
Owner HENAN UNIVERSITY
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com