Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

A kind of hydroxypyridone compound and its preparation method and application

A technology of hydroxypyridones and compounds, applied in the field of medicine, can solve problems such as ineffectiveness and reduced efficacy of antibiotics

Active Publication Date: 2020-06-16
JINAN UNIVERSITY
View PDF1 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the overuse of antibiotics has led to two major clinical problems: one is the increase in bacterial resistance year by year, resulting in reduced efficacy or even ineffectiveness of some antibiotics against certain bacteria (Contemporary Medicine, 2014, 12:295-296), such as Methicillin-resistant Staphylococcus aureus (MRSA), penicillin-resistant Streptococcus pneumoniae (PRSP), vancomycin-resistant Enterococcus (VRE) and multi-resistant Mycobacterium tuberculosis, etc. Bacteria, such as Proteus, Pseudomonas aeruginosa, etc.

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 hydroxypyridone compound and its preparation method and application
  • A kind of hydroxypyridone compound and its preparation method and application
  • A kind of hydroxypyridone compound and its preparation method and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0058] Embodiment 1: the preparation of 5-hydroxyl-2-methyl-4-pyrone (2)

[0059]

[0060] Add kojic acid (50g, 0.35mol) to a 500mL two-necked bottle, add 127mL of SOCl 2 (5eq), stirred at room temperature for 1-2 hours, after the reaction, a yellow solid was obtained, added petroleum ether and stirred for 10-30 minutes, filtered to obtain 56g of filter cake; filter cake (56g, 0.35mol) was dissolved in 200mL water, heated After reaching 50-55°C, add zinc powder (45.5g, 0.70mol), add 105mL of concentrated brine dropwise at 0.5-5mL / min, control the temperature at 70°C-80°C, and react at 70-80°C for 3-5 Hour. Stop the reaction, remove the insoluble matter by hot filtration, extract the filtrate 3 times with dichloromethane, dry the collected dichloromethane with anhydrous sodium sulfate, filter, and concentrate under reduced pressure to obtain the crude product, which is recrystallized with isopropanol / petroleum ether , to obtain white solid compound 2 (37g, 84.1%), melting ...

Embodiment 2

[0062] Embodiment 2: Preparation of 3-hydroxyl-2-(hydroxymethyl)-6-methyl-4-pyrone (3)

[0063]

[0064] Put compound 2 (37g, 0.29mol) in a reaction flask, add NaOH (13g, 0.32mol), add 200mL of water, add 27mL of 35%-38% formaldehyde solution, and stir overnight at room temperature. After the reaction is completed, use 36% concentrated hydrochloric acid to adjust the pH to 1, then cool to 5-0°C and a large amount of solids will precipitate. When the solids no longer precipitate, filter the filter cake and dry the filter cake to obtain white solid compound 3 (42.7g, 93.2%), melting point: 158.3-159.2°C.

[0065] 1 H NMR (300MHz, DMSO-d 6 )δ2.26(s,3H,CH 3 ),4.39(s,2H,CH 2 OH),5.36(brs,1H,CH 2 OH), 6.22(s, 1H, C=CH), 8.87(s, 1H, C=C-OH); 13 C NMR (75MHz, DMSO-d 6 )δ174.36, 165.08, 149.88, 141.73, 111.60, 55.45, 19.75

Embodiment 3

[0066] Example 3: Preparation of 3-(benzyloxy)-2-(hydroxymethyl)-6-methyl-4-pyrone (4)

[0067]

[0068] Compound 3 (42.7g, 0.27mol) was dissolved in 150mL methanol, NaOH (12g, 0.30mol) was added, heated to 75-80°C and refluxed, and benzyl bromide (46.2g, 0.27mol) was added dropwise at 0.5-2mL / min ), reflux reaction at 75-80°C overnight; after the reaction was completed, concentrate under pressure to obtain a residue, dissolve the residue in 200mL water, extract three times with dichloromethane, and wash the collected dichloromethane twice with 5% aqueous sodium hydroxide solution. Washed twice with saturated brine, collected the organic phase, dried over anhydrous sodium sulfate, filtered the crude product concentrated under reduced pressure, and recrystallized the crude product with dichloromethane / petroleum ether to obtain white solid compound 4 (56.6g, 85.2%) , Melting point: 113.2-114.0°C.

[0069] 1 H NMR (300MHz, DMSO-d 6 )δ2.26(s,3H,CH 3 ),4.28(d,2H,J=6.0Hz,CH ...

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

PropertyMeasurementUnit
melting pointaaaaaaaaaa
melting pointaaaaaaaaaa
melting pointaaaaaaaaaa
Login to View More

Abstract

The invention belongs to the field of medicines and discloses novel hydroxypyridinone compounds as well as a preparation method and an application thereof. The compounds have the chemical structure shown in a formula (I), (II) or (III), wherein R1 is propyl, butyl, pentyl, hexyl, heptyl, a hendecanone group, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, furyl, phenyl, p-fluorophenyl, p-trifluoromethylphenyl, p-methoxyphenyl, naphthyl, tolyl, p-chlorotolyl, p-fluorotoyl or methyl cyclohexyl; R2 is caproyl; R3 is phenyl, p-fluorophenyl, p-methylphenyl, p-tert-butylphenyl, p-methoxyphenyl, biphenyl or 1,2,3,4-tetrahydroquinolyl. The novel hydroxypyridinone compounds have bacterial biofilm forming inhibition activity and iron chelating activity and can be applied to preparation of novel drug-resistant bacterium resisting drugs with the bacterial biofilm forming inhibition function.

Description

technical field [0001] The invention belongs to the field of medicine, in particular to a hydroxypyridone compound and its preparation method and application. Background technique [0002] Bacterial infection is a systemic infection caused by pathogenic bacteria or conditional pathogenic bacteria invading the blood circulation to grow and reproduce, producing toxins and other metabolites. Clinically, it is characterized by chills, high fever, rash, arthralgia, and hepatosplenomegaly. There may be septic shock and migratory lesions. Clinically, there are two types of bacterial infection, acute and chronic. Acute bacterial infection can cause acute systemic infection, while chronic bacterial infection often turns into refractory symptoms. Urinary tract infection and wound infection are common clinical chronic bacterial infections, accounting for about 10%-16% of nosocomial infections (Wiley, 2008, pp.pp.73-105). The characteristics of clinical chronic bacterial infection are...

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): C07D213/69C07D405/12C07D401/12A61P31/04
CPCC07D213/69C07D401/12C07D405/12
Inventor 陈卫民林静黎奕斌刘君
Owner JINAN UNIVERSITY
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap 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