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

Oxazolidinone bacteriophage containing azaheterocycle

A technology of isoxazolidoxy and alkyl groups, applied in the field of medicine, can solve the problems of severe, single variety of oxazolidinone antibiotics, and continuous emergence of linezolid resistance.

Active Publication Date: 2011-09-21
BEIJING AOHE DRUG RES INST
View PDF3 Cites 7 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] However, clinically, the drug resistance of Gram-positive bacteria is becoming more and more serious, and the clinical drug variety of oxazolidinone antibiotics is single, which cannot meet the clinical needs, and the drug resistance of linezolid is also emerging

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
  • Oxazolidinone bacteriophage containing azaheterocycle
  • Oxazolidinone bacteriophage containing azaheterocycle
  • Oxazolidinone bacteriophage containing azaheterocycle

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0121] Example 1 (S)-N-[[3-[4-[5-[[(1H-1,2,3-triazol-5-yl)methylamino]methyl]thiophen-2-yl] -3-Fluorophenyl]-2- Preparation of Carbonyloxazolidin-5-yl]methyl]acetamide Hydrochloride (Compound 1 Hydrochloride)

[0122]

[0123] (1) Preparation of N-[(5-bromothiophen-2-yl)methyl]propyn-2-yl-1-amine

[0124]

[0125] In a dry reaction flask, add propargylamine 9.5g (172mmol), 5-bromothiophene-2-carbaldehyde 30g (158mmol) and 1,2-dichloroethane 450mL, stir at room temperature for 2h, then add triethoxy 43.3 g (203 mmol) of sodium borohydride was stirred overnight at room temperature, the reaction solution was washed with water, and the organic phase was directly used in the next step without further treatment.

[0126] (2) Preparation of tert-butyl (5-bromothiophen-2-yl) methyl (propyn-2-yl) carbamate

[0127]

[0128] Add 14.5 g (143 mmol) of triethylamine to the organic solution obtained in the previous step, cool to 0°C, and dropwise add (Boc) 2 O acid anhydride ...

Embodiment 2

[0146] Example 2 (5R)-3-[4-[5-[[(1H-1,2,3-triazol-5-yl)methylamino]methyl]thiophen-2-yl]-3- Fluorobenzene Preparation of -5-(hydroxymethyl)oxazolidin-2-one (compound 4)

[0147]

[0148] (1) tert-butyl[5-[2-fluoro-4-[(R)-5-(hydroxymethyl)-2-oxo-3-oxazolidinyl]phenyl]thiophen-2-yl] Preparation of carbamate

[0149]

[0150] (R)-3-[3-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-5-( Hydroxymethyl) oxazolidin-2-one 8g (23.7mmol), tert-butyl (5-bromothien-2-yl) carbamate 6.9g (23.7mmol), sodium carbonate 5g (47.5mmol), Pd (dppf)Cl 2 Dissolve 0.8g in dioxane, heat to 90°C under the protection of nitrogen and react overnight, cool the reaction solution to room temperature, add water and extract with ethyl acetate, wash the organic layer three times with saline, combine the organic layers, concentrate and pass through the column layer Analysis and separation (DCM:MeOH=20:1) gave 6g of the product.

[0151] (2) Preparation of (R)-3-[4-[5-(aminomethyl)th...

Embodiment 3

[0162] Example 3 (5R)-5-[(1H-1,2,3-triazol-1-yl)methyl]-3-[4-[5-[[(1H-1,2,3- Triazol-5-yl)methylamino] Preparation of methyl]thiophen-2-yl]-3-fluorophenyl]oxazolidin-2-one (compound 5)

[0163]

[0164] (1) (R)-[3-(4-bromo-3-fluorobenzene)-2-carbonyl-oxazolidin-5-yl]methyl 4-methylbenzenesulfonate

[0165]

[0166] Dissolve (R)-3-(4-bromo-3-fluorobenzene)-5-(hydroxymethyl)oxazolidin-2-one (20 g, 69.2 mol) in DCM, add triethylamine (21 g, 207.6mmol) and TosCl (15.8g, 83.1mmol), the reaction solution was stirred overnight at room temperature. The reaction solution was washed with saturated sodium bicarbonate, the organic layer was concentrated to obtain a solid, washed three times with dichloromethane, filtered and dried to obtain a white solid (R)-[3-(4-bromo-3-fluorobenzene)-2-carbonyl-oxane oxazolidin-5-yl]methyl 4-methylbenzenesulfonate 24g.

[0167] (2) (R)-5-(azidomethyl)-3-(4-bromo-3-fluorophenyl)oxazolidin-2-one

[0168]

[0169] (R)-[3-(4-Bromo-3-fluoro...

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 medicaments and in particular relates to oxazolidinone bacteriophage containing azaheterocycle, pharmaceutically-acceptable salts or stereoisomeride thereof, wherein the oxazolidinone bacteriophage is shown as a general formula (I) in the specification, wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, X, Y and Z are defined as a description. The invention also relates to a preparation method of the compound, a medicinal composition containing the compound as well as application of the compound or the medicinal compound thereof to preparation of medicines for treating and / or preventing infectious diseases.

Description

1. Technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to an oxazolidinone antibiotic containing a five-membered heterocycle, a pharmaceutically acceptable salt thereof or a stereoisomer thereof, a preparation method thereof, and a pharmaceutical composition containing the compound , and the application of the compound or its pharmaceutical composition in the preparation of medicines for treating and / or preventing infectious diseases. 2. Background technology [0002] Oxazolidinone antibacterial drugs are a new type of chemically synthesized antibacterial drugs developed after sulfonamides and fluoroquinolones, which can inhibit multi-drug resistant Gram-positive bacteria. [0003] Linezolid is the first marketed oxazolidinone antibiotic. [0004] [0005] It has a strong inhibitory effect on Gram-positive bacteria and has no cross-resistance with other antibacterial drugs. Its unique mechanism of action inhibits th...

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): C07D413/14C07D417/14A61K31/497A61K31/4439A61K31/427A61K31/422A61P31/00
Inventor 黄振华宋运涛
Owner BEIJING AOHE DRUG RES INST
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