Unlock instant, AI-driven research and patent intelligence for your innovation.

Phosphorylation cephalosporin derivates

A compound, phosphono technology, applied in the field of medicine, can solve the problems of strong bacterial resistance and affecting the antibacterial efficacy of cephalosporins

Active Publication Date: 2009-04-29
JILIN SIHUAN PHARM CO LTD
View PDF0 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] However, due to the widespread use or even abuse of antibiotics in clinical practice, bacterial drug resistance is becoming stronger and stronger, which greatly affects the antibacterial efficacy of cephalosporin antibiotics

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
  • Phosphorylation cephalosporin derivates
  • Phosphorylation cephalosporin derivates
  • Phosphorylation cephalosporin derivates

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0092] Embodiment 1 Preparation of Compound 1 of the present invention and its sodium salt

[0093] Step 1: Preparation of diisopropyl phosphite

[0094] Add 240ml of anhydrous isopropanol and 40ml of toluene into a 500ml four-necked bottle, control the temperature in an ice-water bath below 15°C, and add 70ml of phosphorus trichloride (PCl 3 ) within 4 hours, the temperature was raised to 50-60°C, and the reaction was continued for 6 hours. At the same time, the hydrogen chloride gas generated in the system was extracted under reduced pressure, concentrated under reduced pressure, and the concentrated liquid was rectified, collected at 62-67°C / 0.095 The fraction of MP can be obtained.

[0095] Step 2: Preparation of compound 1 of the present invention

[0096] Under ice-salt bath, control the temperature at about 0°C, add 26.5g (45mmol) of cefodizime acid into a 1000ml four-neck bottle, add 200ml of water, stir, adjust the pH to 9.5 with 25% sodium hydroxide solution, and...

Embodiment 2

[0107] Embodiment 2 Preparation of Compound 2 of the present invention and its sodium salt

[0108] Step 1: Preparation of diethyl phosphite

[0109] Add 230ml of absolute ethanol and 50ml of carbon tetrachloride into a 1000ml four-necked bottle, control the temperature in an ice-water bath below 15°C, and add 88ml of phosphorus trichloride (PCl 3 ) was added within 4 hours, heated to 50-60°C, and continued to react for 6 hours. At the same time, the hydrogen chloride gas generated in the system was extracted under reduced pressure, concentrated under reduced pressure, and the concentrated liquid was rectified, collected at 89-93°C / 0.095 The fraction of MP can be obtained.

[0110] Step 2: Preparation of compound 2 of the present invention

[0111] Under ice-salt bath, control the temperature at about 0°C, add 26.5g (45mmol) of cefodizime acid into a 1000ml four-neck bottle, add 200ml of water, stir, adjust the pH to 9.5 with 25% sodium hydroxide solution, and the solids a...

Embodiment 3

[0122] Embodiment 3 Preparation of Compound 3 of the present invention and its sodium salt

[0123] Step 1: Preparation of compound 3 of the present invention

[0124] Under ice-salt bath, control the temperature at about 0°C, add 26.5g (45mmol) of cefodizime acid into a 1000ml four-neck bottle, add 200ml of water, stir, adjust the pH to 9-10 with 25% sodium hydroxide solution, solid Completely dissolve, add 108mg tetrabutylammonium bromide and 4.2g (50mmol) phosphorous acid, dropwise add 22.5ml concentration and be 12% sodium hypochlorite solution. After addition, the reaction was continued for 4 hours. Stop the reaction, add diethyl ether to extract once, lower the pH of the aqueous layer to 3 with hydrochloric acid in an ice bath, freeze and crystallize, filter, wash the filter cake with ethanol, filter, and dry the filter cake at 40°C for 8 hours under reduced pressure to obtain a light yellow powder 26.5 g, yield: 78.5%.

[0125] Molecular formula: C 20 h 21 N 6 o...

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 medicine, and in particular relates to phosphorylated cephalosporin derivatives of a general formula (I), pharmaceutically acceptable salts, easily hydrolysable esters and isomers of the phosphorylated cephalosporin derivatives, wherein R<1>, R<2>, R<3>, R<4> and R<5> are as defined in the specification. The invention also relates to methods for preparing the compounds, pharmaceutical compositions of the compounds, and use of the compounds for the preparation of drugs for treating and / or preventing in infectious diseases.

Description

1. Technical field [0001] The present invention relates to phosphonylated cephalosporin derivatives, pharmaceutically acceptable salts thereof, easily hydrolyzed esters or isomers thereof, preparation methods of these compounds, pharmaceutical compositions containing these compounds, and preparation of these compounds for use in The use in medicine for treating and / or preventing infectious diseases belongs to the technical field of medicine. 2. Background technology [0002] Cephalosporin antibiotics are antibiotics widely used clinically and have been developed into four generations. [0003] Cefodizime (Cefodizime) is a parenteral broad-spectrum third-generation cephalosporin, which has antibacterial activity against Gram-positive bacteria and negative bacteria, and has good stability against most β-lactamases. Bacterinase and penicillinase are extremely stable. In vitro against Staphylococcus aureus (with the exception of methicillin-resistant strains), Streptococcus pn...

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): C07F9/6561C07D501/36A61K31/66A61K31/546A61P31/04
Inventor 黄振华
Owner JILIN SIHUAN PHARM CO LTD