C3/C3 fluoroquinolone dimmer derivative using oxadiazole as connection chain as well as preparation method and application thereof

A technology of quinolone dimer and oxadiazole, which is applied in the field of pharmaceutical chemical synthesis, can solve the problems that have not been reported, and achieve the effects of strong anti-tumor activity, strong growth inhibitory activity, and strong cytotoxicity

Inactive Publication Date: 2010-02-10
河南省健康伟业生物医药研究股份有限公司
View PDF1 Cites 67 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Existing FQ anti-tumor compounds all contain one FQ unit, and compounds containing two FQ structural units in one molecule have not been reported yet. In

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
  • C3/C3 fluoroquinolone dimmer derivative using oxadiazole as connection chain as well as preparation method and application thereof
  • C3/C3 fluoroquinolone dimmer derivative using oxadiazole as connection chain as well as preparation method and application thereof
  • C3/C3 fluoroquinolone dimmer derivative using oxadiazole as connection chain as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] Preparation of 1-ethyl-6-fluoro-7-piperazin-1-yl-4(1H)-quinolinone-3-carboxhydrazide (norfloxacin hydrazide 1)

[0039] Norfloxacin (50 g, 157 mmol) was dissolved in 100 mL of 80% hydrazine hydrate, refluxed for 18 hours, cooled to room temperature, distilled under reduced pressure until evaporated to dryness, and the residue was recrystallized with 300 mL of absolute ethanol to obtain a yellow solid 1, Yield 74%. mp 186~187℃; IR(KBr)v: 3456, 2897, 1648, 1567, 1527, 1473, 1255, 869cm -1 ; 1 H NMR (DMSO-d 6 )δ: 10.56 (brs, 1H, CONH), 8.86 (s, 1H, 2-H), 7.86 (d, 1H, 5-H), 7.24 (d, 1H, 8-H), 4.53 (brs, 2H , NH 2 ), 4.62 (q, 2H, NCH 2 ), 3.32(t, 4H, piperazine-H), 2.67(t, 4H, piperazine-H), 1.36(t, 3H, CH 3 ); MS m / z: 356 (M+Na), 334 (M+H); Anal.calcd for C 16 h 20 FN5 o 2 : C 57.65, H 6.05, N 21.01; found C 57.84, H 6.15, N 21.24.

Embodiment 2

[0041] Preparation of 1-ethyl-6-fluoro-7-(4-methylpiperazin-1-yl)-4(1H)-quinolinone-3-carboxhydrazide (pefloxacin hydrazide 2)

[0042] Using pefloxacin as raw material, compound 2 was obtained by the same preparation method as in Example 1, with a yield of 68%. mp192~194℃; IR(KBr)v: 3387, 3025, 1638, 1557, 1525, 1456, 1255, 886cm -1 ; 1 H NMR (DMSO-d 6 )δ: 10.46 (brs, 1H, CONH), 8.87 (s, 1H, 2-H), 7.82 (d, 1H, 5-H), 7.32 (d, 1H, 8-H), 4.56 (brs, 2H , NH 2 ), 4.42 (q, 2H, NCH 2 ), 3.35(t, 4H, piperazine-H), 2.66(t, 4H, piperazine-H), 2.37(s, 3H, N-CH 3 ), 1.34(t, 3H, CH 3 ); MS m / z: 348 (M+H); Anal.calcd for C 17 h 22 FN 5 o 2 : C58.78, H 6.38, N 20.16; found C 58.94, H 6.20, N 20.40.

Embodiment 3

[0044] Preparation of 1-cyclopropyl-6-fluoro-7-piperazin-1-yl-4-(1H)-quinolinone-3-carboxhydrazide (ciprofloxacin hydrazide 3)

[0045] Using ciprofloxacin as raw material, compound 3 can be obtained according to the same preparation method as in Example 1, with a yield of 70%. mp226~227℃; IR(KBr)v: 3428, 3309, 2940, 2834, 1661, 1626, 1471cm -1 ; 1 H NMR (DMSO-d 6 )δ: 1.20~1.35(m, 4H, cyclopropane-H), 3.09~3.12(m, 4H, piperazine-H), 3.25~3.27(m, 4H, piperazine-H), 3.45~3.51(m, 1H , cyclopropane-H), 4.45 (brs, 2H, NH 2 ), 7.32(d, 1H, 8-H), 8.01(d, 1H, 5-H), 8.77(s, 1H, 2-H), 10.83(s, 1H, CONH); MS m / z: 346 (M+H); Anal.calcd for C 17 h 20 FN 5 o 2 : C 59.12, H 5.84, N 20.28; found C 59.36, H 5.67, N 20.46.

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 C3/C3 fluoroquinolone dimmer derivative using oxadiazole as a connection chain as well as a preparation method and an application thereof. The C3/C3 fluoroquinolone dimmer derivative using oxadiazole as a connection chain is a compound which has the following structural general formula (I), wherein R1 and R1' are independently selected from H, (C1-C10) alkyl, (C3)-(C10) cycloalkyl, (C1)-(C10) haloalkyl and substituted aryl group or substituted heterocyclic aryl group; R2 and R2' are independently selected from H, (C1-C7)alkyl, (C3)-(C7) cycloalkyl, substituted aryl group, substituted heterocyclic aryl group and hydrocarbon acyl or sulfonyl; R3 and R3' are independently selected from H, (C1-C5) alkyl, (C3)-(C5) cycloalkyl, substituted aryl radical or substitutionalheterocyclic aryl radical; and X and Y are independently selected from CH, N or carbon atoms connected with halogen, alkyl, oxyl, sulfenyl, amino, substituted amino, substituted aryl radical or substituted heterocyclic aryl radical. The C3/C3 fluoroquinolone dimmer derivative using oxadiazole as a connection chain can be used for preparing medicaments for treating tumors and preventing microbialinfection diseases.

Description

technical field [0001] The invention relates to the technical field of pharmaceutical chemical synthesis, in particular to a C3 / C3 fluoroquinolone dimer derivative with oxadiazole as a linking chain, a preparation method thereof, and an application as a medicine for preparing tumors and antimicrobial infection diseases. Background technique [0002] Fluoroquinolones (FQ) are clinical antimicrobials developed in the 1980s, represented by norfloxacin, and nearly 30 varieties have been widely used clinically. The action target of fluoroquinolones topoisomerase (TOPO) has homologous sequence similarity with TOPO of mammals, and TOPO is also a new target of antitumor drug action. Accordingly, it is important to convert antibacterial drug FQ into antitumor drug FQ A new direction of current research. At present, anti-tumor FQ compounds including bicyclic quinolones, tricyclic quinolones, tetracyclic quinolones, chiral quinolones, flavonoids and other anti-tumor FQ compounds have ...

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
IPC IPC(8): C07D413/14C07D498/06C07D513/06C07D519/00A61K31/496A61K31/5383A61K31/542A61P35/00A61P31/00
Inventor 胡国强谢松强侯莉莉孙茂峰张俊珂杨勇伊磊
Owner 河南省健康伟业生物医药研究股份有限公司
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
Try Eureka
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap