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

Cephalosporin antibiotic derivant

A compound and hydrate technology, applied in the field of medicine, can solve the problem of low sensitivity

Active Publication Date: 2008-08-20
北京锐业制药有限公司
View PDF0 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] However, the above-mentioned third-generation or fourth-generation cephalosporin antibiotics have very low susceptibility to methicillin-resistant staphylococcus, which is currently clinically highly resistant, so it is urgent to develop a new drug with high efficacy against drug-resistant bacteria

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
  • Cephalosporin antibiotic derivant
  • Cephalosporin antibiotic derivant
  • Cephalosporin antibiotic derivant

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0122] The preparation of embodiment 1 heterocycle

[0123] 1, the preparation of 2-(3-mercapto-azetidin-1-yl)-4,5-dihydroazole

[0124] In the reaction flask, add 35.2g (0.3mol) of 3-formylmercapto-azetidine and 500ml tetrahydrofuran, stir to dissolve, add 40g of powdery potassium carbonate, heat up to reflux, drop 2-bromo-4, 58.1g (0.35mol) / 200ml of 5-dihydrothiazole in tetrahydrofuran solution, after the dropwise addition, keep stirring and react for 2h, filter the reaction solution, concentrate to dryness under reduced pressure, add 200ml of 4mol / L hydrochloric acid, stir at room temperature for 2h, Adjust the pH above 8 with a dilute alkali solution, and a yellow solid precipitates out. The solid is purified with a methanol / acetone mixed solution, and the light yellow solid is 42.4 g, with a yield of 81%.

[0125] 2. Preparation of N-3-methyl-2-(3-mercapto-azetidin-1-yl)-4,5-dihydrothiazole chloride

[0126] In the reaction flask, add 35.2g (0.3mol) of 3-formylmercapt...

Embodiment 2

[0129] The preparation of embodiment 2 intermediate

[0130] 1. (6R,7R)-7-phenylacetamido-3-[[N-1-(4,5-dihydrothiazol-2-yl)-azetidin-3-yl]thio] Preparation of 8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid diphenylmethyl ester

[0131] In a dry reaction flask, (6R,7R)-7-phenylacetamido-3-hydroxy-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene- 50g (0.1mol) of diphenylmethyl 2-formate was dissolved in 300ml of dry acetone, 20ml of diisopropylethylamine was added dropwise at -15°C, and then 9ml of methanesulfonyl chloride was slowly added dropwise. Stir the reaction at ℃ for 1 h. After the reaction is completed, pour the reaction liquid into water, collect the precipitate, wash it with water, dry it fully, and put it into the next step directly.

[0132] Put 17.4 g (0.1 mol) of 2-(3-mercapto-azetidin-1-yl)-4,5-dihydrothiazole into a dry reaction flask, then add 200 ml of tetrahydrofuran solution, and then add powder Sodium carbonate 20g, add (6R, 7R)-7-phenylacetamid...

Embodiment 3

[0149] The preparation of embodiment 3 compounds of the present invention

[0150] 1. (6R,7R)-7-[[2-(5-Amino-1,2,4-thiadiazol-3-yl)-Z-2-methoximino]acetamido]-3- [[N-1-(4,5-dihydrothiazol-2-yl)-azetidin-3-yl]thio]-8-oxo-5-thia-1-azabicyclo [4.2.0] Preparation of oct-2-ene-2-carboxylic acid (i.e. compound 1-1)

[0151] Add (6R,7R)-7-amino-3-[[N-1-(4,5-dihydrothiazol-2-yl)-azetidin-3-yl]sulfanyl to a dry reaction flask ]-8-Oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid diphenylmethyl ester is 18.1g (25mmol), anisole 40ml, in stirring , add 80ml of trifluoroacetic acid under cooling in an ice bath, stir at 10-15°C for 1.5h, after the reaction is complete, pour the reaction solution into 500ml of petroleum ether, filter, dissolve the filter cake in 200ml of absolute ethanol, wash with saturated sodium bicarbonate The solution was adjusted to pH 5-6, filtered, and the filter cake was washed twice with a small amount of acetone to obtain (6R, 7R)-7-[[2-(5-amino-1,2,4...

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 medicine and discloses a cephalosporin antibiotics derivative which has antibiotic activity and is shown in the general formula (I), the pharmacologically acceptable salt, the easily hydrolysable ester, the hydrate, and the hydrate of the ester or the salt; wherein, R<1>, R<2>, R<3>, R<4>, R<5> and X are defined in the instruction book, in addition, the invention further provides the preparation methods of the compounds, the medicine combinations containing the compounds, and the application of the compounds in the 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 cephalosporin derivatives, pharmaceutically acceptable salts thereof, easily hydrolyzed esters, hydrates thereof and hydrates of esters or salts thereof, preparation methods of these compounds, and preparations containing these compounds Pharmaceutical compositions, and the use of these compounds in the preparation of medicines for treating and / or preventing infectious diseases. 2. Background technology [0002] Cephalosporin antibiotics have been widely used in the treatment of various infectious diseases caused by pathogenic bacteria, especially for the treatment of various bacteria resistant to penicillin and for the treatment of patients allergic to penicillin. People have carried out extensive research on cephalosporin antibiotics with a broad spectrum. After a large number of studies, it has been found that the introduction of 2-(2-aminothiazol-4-yl)-2-hydro...

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): C07D501/59A61K31/546A61P31/04
CPCY02P20/55
Inventor 黄振华
Owner 北京锐业制药有限公司