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

[2-(1H)-quinolinone-3-yl]aminomethylphosphonate, and preparation method and application thereof

A technology of aminomethylphosphonate and diethyl anilinomethylphosphonate is applied in pharmaceutical formulations, medical preparations containing active ingredients, organic active ingredients, etc. restrictions, and the development of drug resistance

Inactive Publication Date: 2016-10-05
HUNAN UNIV
View PDF6 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

M2 ion channel inhibitors are prone to drug resistance, have serious side effects on the gastrointestinal tract and central nervous system, and are only effective for type A, so their clinical application is greatly limited

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
  • [2-(1H)-quinolinone-3-yl]aminomethylphosphonate, and preparation method and application thereof
  • [2-(1H)-quinolinone-3-yl]aminomethylphosphonate, and preparation method and application thereof
  • [2-(1H)-quinolinone-3-yl]aminomethylphosphonate, and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0027] Preparation of [2-(1H)-quinolinone-3-yl]anilinomethylphosphonic acid diethyl ester

[0028]

[0029] (1) Preparation of 3-formyl-2-(1H)-quinolinone

[0030] 98ml POCl 3 Add dropwise to 7ml of N,N-dimethylformamide, stir at 0-5°C for 30min, add 50mmol of acetanilide, raise the temperature to 90°C, and react for 16h. After cooling, the reaction was also poured into 500ml of ice water, filtered with suction, and washed with water. Add 200ml of 70% acetic acid solution to the solid, and react at 95°C for 4h. After cooling the reaction solution, flocculent solids were precipitated, filtered, washed with water, and dried to obtain 3-formyl-2-(1H)-quinolinone with a yield of 73.8%, m.p.303-305°C.

[0031] (2) Preparation of [2-(1H)-quinolinone-3-yl]anilinomethylphosphonic acid diethyl ester

[0032]2mmol 3-formyl-2-(1H)-quinolinone, 2mmol aniline and 15ml toluene, stirred at room temperature for 10min, added 2mmol diethyl phosphite, refluxed for 4h (monitored by TLC), c...

Embodiment 2

[0034] Preparation of [2-(1H)-quinolinone-3-yl]benzylaminomethylphosphonic acid diethyl ester

[0035]

[0036] 2mmol 3-formyl-2-(1H)-quinolinone, 2mmol benzylamine and 15ml toluene, stirred at room temperature for 10min, added 2mmol diethyl phosphite, refluxed for 1h (monitored by TLC); 石油醚 :V 乙酸乙酯 =1:1 Column chromatography, drying to give [2-(1H)-quinolinon-3-yl]benzylaminomethylphosphonic acid diethyl ester, yield 67.5%, m.p.113-116°C. 1 H NMR (400MHz, CDCl 3 )δ: 12.34(s, 1H, NH), 8.10(d, J=3.2Hz, 1H), 7.61(d, J=7.6Hz, 2H), 7.51(t, J=7.6Hz, 1H), 7.40( d, 1H, J=8.4Hz, 1H), 7.65(d, J=7.6Hz, 1H), 7.34~7.26(m, 4H), 7.24~7.21(m, 2H), 4.80~4.75(m, 1H, NCHP), 4.32~4.20(m, 2H, OCH 2 ), 4.11~4.00 (m, 2H, OCH 2 ), 3.90~3.69 (m, 2H, CH 2 ), 1.32(t, J=6.8Hz, 3H, CH 3 ), 1.18(t, J=6.8Hz, 3H, CH 3 ); 13 C NMR (100MHz, CDCl 3 )δ: 163.61, 139.44, 138.01, 130.53, 128.40, 128.35, 127.95, 127.12, 122.69, 119.92, 115.96, 109.38, 63.46, 62.88, 51.97, 51.82, 18.35, 16.351, and 16. ...

Embodiment 3

[0038] Preparation of [2-(1H)-quinolinone-3-yl]-2-methylanilinomethylphosphonic acid diethyl ester

[0039]

[0040] 2mmol 3-formyl-2-(1H)-quinolinone, 2mmol 2-methylaniline and 15ml toluene, stirred at room temperature for 10min, added 2mmol diethyl phosphite, refluxed for 3h (monitored by TLC); 石油醚 :V 乙酸乙酯 =1:1 column chromatography, dried to give [2-(1H)-quinolinon-3-yl]-2-methylanilinomethylphosphonic acid diethyl ester, yield 86.3%, m.p.191~193℃ . 1 H NMR (400MHz, CDCl 3 )δ: 11.59(s, 1H, NH), 8.01(d, J=3.6Hz, 1H), 7.54(d, J=7.9Hz, 1H), 7.49(t, J=7.6Hz, 1H), 7.20( t, J=7.4Hz, 1H), 7.05(d, J=7.2Hz, 1H), 6.97(t, J=7.7Hz, 1H), 6.65(t, J=7.3Hz, 1H), 6.58(d, J=8.0Hz, 1H), 5.56~5.50(m, 1H, NCHP), 4.86(s, 1H, NH), 4.31~4.26(m, 2H, OCH 2 ), 4.14~3.99 (m, 2H, OCH 2 ), 2.30 (s, 3H, CH 3 ), 1.34(t, 3H, J=7.0Hz, CH 3 ), 1.15(t, 3H, J=6.9Hz, CH 3 ); 13 C NMR (100MHz, CDCl 3 )δ:163.37、143.92、138.35、138.02、130.58、130.30、128.49、128.17、127.23、123.02、122.78、119.98、118.31、115.8...

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 relates to [2-(1H)-quinolinone-3-yl]aminomethylphosphonate represented by a chemical structural formula I, or a salt thereof. In the formula, R is selected from C1-C2 alkyl and C3-C4 straight-chain alkyl or branched-chain alkyl; X1 and X2 are selected from hydrogen, deuterium and C1-C2 alkyl; X3 and X7 are selected from hydrogen, deuterium, C1-C2 alkyl, fluoro, chloro, bromo, iodo and nitro; X4 and X6 are selected from hydrogen, deuterium and C1-C2 alkyl; X5 is selected from hydrogen, deuterium, C1-C2 alkyl and nitro; and n=0 or 1. The invention also relates to an application of [2-(1H)-quinolinone-3-yl]aminomethylphosphonate or the salt thereof in preparing neuraminidase inhibitors.

Description

technical field [0001] The invention relates to the preparation and application of a class of novel compounds; specifically, the preparation of [2-(1H)-quinolinone-3-yl]aminomethylphosphonate and its application as an influenza virus neuraminidase inhibitor. Background technique [0002] Avian influenza virus (AIV) belongs to type A influenza virus and can be divided into 16 H (H 1 -H 16 ) subtypes and nine N(N 1 -N 9 ) subtype, among many subtypes of influenza A virus, H 5 and H 7 highly pathogenic avian influenza virus. H 5 N 1 、H 7 N 2 、H 7 N 3 、H 7 N 7 、H 9 N 2 、H 10 N 7 、H 7 N 9 And in December 2013, a new bird flu H was discovered in Jiangxi, my country 10 N 9 Subtype. Symptoms of these subtypes vary and can mainly manifest as respiratory symptoms, conjunctivitis, and even death. Highly pathogenic H 5 N 1 Subtype and the new avian influenza H first detected in humans in March 2013 7 N 9 Subtypes are of particular interest. [0003] In 1997, ...

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 Applications(China)
IPC IPC(8): C07F9/60A61K31/675A61P31/16
Inventor 胡艾希方毅林李水师叶姣刘艾林连雯雯
Owner HUNAN UNIV
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