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

4-hydroxy-2-quinolone-nitrogen-(4-quinazolinone)-3-formamide derivatives

A technology of quinazolinone and formamide, applied in the field of antibacterial drugs

Active Publication Date: 2019-07-23
INST OF MATERIA MEDICA AN INST OF THE CHINESE ACAD OF MEDICAL SCI
View PDF1 Cites 5 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Up to now, the compounds involved in this patent have not been reported at home and abroad to inhibit the growth of bacteria, so this series of compounds belong to the leading structure of antibacterial drugs of new structure type

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
  • 4-hydroxy-2-quinolone-nitrogen-(4-quinazolinone)-3-formamide derivatives
  • 4-hydroxy-2-quinolone-nitrogen-(4-quinazolinone)-3-formamide derivatives
  • 4-hydroxy-2-quinolone-nitrogen-(4-quinazolinone)-3-formamide derivatives

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0074] Embodiment 1: Preparation and detection of compound XWJ-10

[0075]

[0076] Add 1.64mL (12mmol) of triethylamine to the DMF solution of 2.11g (10mmol) of methyl 2-amino-3,4-dimethoxybenzoate, add hexanoyl chloride (12mmol) dropwise at 0°C, and drop to room temperature The reaction was stirred and reacted for 3 hours. After the reaction was monitored by TLC, the reaction solution was poured into ice water, and a solid was precipitated, which was filtered by suction and dried. The obtained solid was dissolved in absolute ethanol, and 3 mL of 80% hydrazine hydrate (36 mmol) was added, and the reflux reaction was carried out for 8 After cooling for a few hours, the solid was precipitated, filtered with suction, and dried to obtain 1.82 g of the intermediate 3-amino-6,7-dimethoxy-2-pentyl-4-quinazolinone (yield: 62.5%).

[0077] 12.8mL (73.6mmol) of diisopropylethylamine was added to the DMF solution of 10g (61.3mmol) isatoic anhydride, and 9.6g (73.6mmol) ethyl iodide w...

Embodiment 2

[0082] Embodiment 2: Preparation and detection of compound XWJ-1

[0083] Using 2-amino-5-chlorobenzoic acid methyl ester and hexanoyl chloride as starting materials, the synthesis method is the same as that of the intermediate 3-amino-6,7-dimethoxy-2-pentyl-4-quinazolinone , to obtain the intermediate 3-amino-6-chloro-2-pentyl-4-quinazolinone (yield: 72.9%).

[0084] Using 3-amino-6-chloro-2-pentyl-4-quinazolone and 1-ethyl-4-hydroxy-2-quinolone-3-carboxylic acid as starting materials, the synthesis method is the same as the final product XWJ-10 The preparation of 1-ethyl-4-hydroxyl-2-quinolone-nitrogen-(6-chloro-2-pentyl-4-quinazolinone-3-yl)-3-formamide (XWJ-1) .

[0085]

[0086] White solid, yield 19.1%. 1 H NMR (500MHz, DMSO-d 6 )δ8.06(s,1H),8.19(d,J=8.0Hz,1H),7.81(d,J=8.6Hz,1H),7.67(d,J=8.6Hz,1H),7.64(t, J=7.8Hz, 1H), 7.53(d, J=7.9Hz, 1H), 7.24(t, J=7.5Hz, 1H), 4.23(q, J=7.3Hz, 2H), 2.95(t, J= 7.8Hz, 2H), 1.79(p, J=6.9Hz, 2H), 1.41-1.36(m, 4H), 1.19(t, J=7.1Hz,...

Embodiment 3

[0087] Embodiment 3: Preparation and detection of compound XWJ-2

[0088] Using methyl 2-amino-5-bromobenzoate and hexanoyl chloride as starting materials, the synthesis method is the same as that of the intermediate 3-amino-6,7-dimethoxy-2-pentyl-4-quinazolinone , to obtain the intermediate 3-amino-6-bromo-2-pentyl-4-quinazolinone (yield: 63.2%).

[0089] Using 3-amino-6-bromo-2-pentyl-4-quinazolone and 1-ethyl-4-hydroxy-2-quinolone-3-carboxylic acid as starting materials, the synthesis method is the same as the final product XWJ-10 The preparation of 1-ethyl-4-hydroxyl-2-quinolone-nitrogen-(6-bromo-2-pentyl-4-quinazolinone-3-yl)-3-formamide (XWJ-2) .

[0090]

[0091] Brown solid, yield 24.1%. 1 H NMR (500MHz, DMSO-d 6 )δ8.30(d, J=2.5Hz, 1H), 8.18(d, J=8.0Hz, 1H), 7.93(dd, J=8.6, 2.4Hz, 1H), 7.64(t, J=7.8Hz, 1H), 7.54(d, J=7.9Hz, 1H), 7.52(d, J=8.7Hz, 1H), 7.54(d, J=7.9Hz, 1H), 7.24(t, J=7.5Hz, 1H) ,4.23(q,J=7.3Hz,2H),2.98-2.91(m,2H),1.79(p,J=7.4Hz,2H),1.43-1.35(m,4...

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 belongs to the technical field of antibacterial drugs and relates to 4-hydroxy-2-quinolone-nitrogen-(4-quinazolinone)-3-formamide derivatives as well as a preparation method and an application thereof as an antibacterial drug. The compounds are shown in a formula (I), wherein R1 is selected from hydrogen, trifluoromethyl, C1-C8 alkyl, C1-C8 alkoxy and halogen; R2 is selected from hydrogen, nitryl, C1-C8 alkyl, C1-C8 alkoxy and halogen; R3 is selected from C1-C8 alkyl and aryl methyl; R4 is selected from C1-C8 alkyl. The 4-hydroxy-2-quinolone-nitrogen-(4-quinazolinone)-3-formamidederivatives are first discovered antibacterial compounds of novel structures, the compounds have higher inhibition functions on gram-positive bacteria including staphylococcus aureus, staphylococcusepidermidis, enterococcus and the like, particularly, drug-resistant gram-positive bacteria (MRSA (methicillin-resistant staphylococcus aureus), MRSE (methicillin-resistant staphylococcus epidermidis)and VRE (vancomycin-resistant enterococci)) and can be used for following further modification and development.

Description

technical field [0001] The invention belongs to the technical field of antibacterial drugs, and specifically relates to 4-hydroxy-2-quinolone-nitrogen-(4-quinazolinone)-3-carboxamide derivatives, a preparation method and an application as antibacterial drugs. Background technique [0002] Bacterial infection is an infection caused by pathogenic bacteria or conditional pathogenic bacteria invading the body to grow and reproduce, producing toxins and other metabolites. Bacterial infection is one of the main factors that endanger human health, and the emergence of bacterial drug resistance in recent years has made the challenge of global public health more severe. Among resistant Gram-positive bacteria, methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant surface Staphylococcus (MRSE), and vancomycin-resistant enterococci (VRE) were the most common. The discovery of antibacterial drugs with new structures or new mechanisms of action has important clinical ...

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): C07D401/12A61K31/517A61P31/04
CPCC07D401/12A61P31/04
Inventor 吴松夏杰薛文杰冯波
Owner INST OF MATERIA MEDICA AN INST OF THE CHINESE ACAD OF MEDICAL SCI
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