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

Formamide alkylbenzene substituted mercapto pyrrolidine carbapenem compounds

A compound, methyl technology, applied in the field of mercaptopyrrolidine carbapenem compounds substituted by carboxamide alkylbenzene, can solve the problems of not meeting clinical needs, low clinical utilization, and weak antibacterial activity of MRSA

Active Publication Date: 2011-05-18
XUANZHU BIOPHARMACEUTICAL CO LTD
View PDF2 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] Due to the continuous increase of bacterial resistance and the limitation of digestive tract absorption due to the abuse of antibiotics, the carbapenems currently on the market can only be administered as injections in clinical practice, and the clinical utilization is not high, and the antibacterial activity against MRSA Weak, can no longer meet clinical needs

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
  • Formamide alkylbenzene substituted mercapto pyrrolidine carbapenem compounds
  • Formamide alkylbenzene substituted mercapto pyrrolidine carbapenem compounds
  • Formamide alkylbenzene substituted mercapto pyrrolidine carbapenem compounds

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0091] Preparation of Example 1 (2S, 4S)-4-mercapto-2-formyl [N-benzyl-2-methylpropyl-2-amino]-1-(tert-butoxycarbonyl)pyrrolidine

[0092] 14.5 g (50 mmol) of (2S,4S)-4-acetylthio-2-carboxy-1-(tert-butoxycarbonyl)pyrrolidine and 150 ml of anhydrous tetrahydrofuran were added to a dry reaction flask. Under the protection of nitrogen, add 13g (80mmol) of 1,1-carbonyldiimidazole at room temperature, react for 0.5h, add 8.3g (51mmol) of N-benzyl-2-methylpropyl-2-amine below 0°C Tetrahydrofuran solution 100ml, continue to react for 1h. Then 60ml of 1mol / L hydrochloric acid was added dropwise, extracted with ethyl acetate (100ml×2), the organic phase was washed with water and saturated sodium chloride solution successively, concentrated under reduced pressure, the residue was added with 150ml of 3mol / L hydrochloric acid, stirred for 2h, and The dilute alkali solution was adjusted to be alkaline, and a solid was precipitated, which was recrystallized from an acetonitrile solution ...

Embodiment 2

[0093] Example 2 (2S, 4S)-4-mercapto-2-formyl [N-(4-fluorobenzyl)-2-methylpropyl-2-amino]-1-(tert-butoxycarbonyl)pyrrole Preparation of alkane

[0094] Refer to Example 1 for the specific preparation method. Cast (2S, 4S)-4-acetylthio-2-carboxy-1-(tert-butoxycarbonyl)pyrrolidine 14.5g (50mmol), N-(4-fluorobenzyl)-2-methylpropyl- 2-amine 9.2 g (51 mmol). 16.3 g of the product was obtained, yield: 79.3%.

Embodiment 3

[0095] Example 3 (4R, 5S, 6S)-3-[(2S, 4S)-2-formyl[N-benzyl-2-methylpropyl-2-amino]-1-(tert-butoxycarbonyl )pyrrolidin-4-yl]thio-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3,2,0]hept 2-ene - Preparation of p-nitrobenzyl 2-carboxylate

[0096] In a dry reaction flask, add (4R, 5S, 6S)-3-diphenoxyphosphoryloxy-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1- Azabicyclo[3,2,0]hept-2-ene-2-carboxylic acid p-nitrobenzyl ester 11.9g (20mmol) in 120ml of acetonitrile solution, cooled to below -10°C, add 5ml of diisopropylethylamine and (2S, 4S)-4-mercapto-2-formyl [N-benzyl-2-methylpropyl-2-amino]-1-(tert-butoxycarbonyl)pyrrolidine 8.6g (22mmol) Acetonitrile solution 80ml, stirred at 0°C for 15h. After the reaction was completed, 300 ml of ethyl acetate was added to dilute, washed with water and saturated brine in sequence, the organic layer was dried and concentrated to obtain 10.1 g of solid, yield: 68.3%.

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 a formamide alkylbenzene-substituted sulfhydryl pyrrolidine carbapenem compound as shown in general formula (I), and also relates to the easy hydrolysis esters of the compound, the pharmaceutical acceptable non-toxic salts of the compound, the isomers of the compound, the hydrates of the compound, the hydrates of the esters or salts of the compound, the preparation methods for the compounds in formula (I), the purposes of the compounds as medicinal active substances and especially the applications of the compounds in the preparation of drugs for curing and / or preventing infectious diseases, as well as the drug combinations containing the compounds in formula (I). The detailed definitions of R<1>, R<2>, R<3>, R<4>, R<5>, R<6> and n in the formula (I) are shown in the specification.

Description

1. Technical field [0001] The present invention relates to carboxamide alkylbenzene-substituted mercaptopyrrolidine carbapenem compound, its easily hydrolyzed ester, its pharmaceutically acceptable non-toxic salt, its isomer, its hydrate, and its ester or salt The hydrate, the preparation method of these compounds, the pharmaceutical composition containing these compounds, and the application of these compounds in the preparation of medicines for treating and / or preventing infectious diseases belong to the technical field of medicine. 2. Background technology [0002] Carbapenems are new broad-spectrum, enzyme-resistant and highly effective β-lactam antibiotics developed in the 1970s. In 1976, Thiamycin, the first carbapenem antibiotic, was discovered, but it was not used clinically due to its poor chemical stability. Later, the chemical structure modification of thiamycin produced a series of carbapenem derivatives. At present, such drugs that have been marketed include i...

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 Patents(China)
IPC IPC(8): C07D477/20A61K31/407A61P31/00
CPCY02P20/55
Inventor 黄振华
Owner XUANZHU BIOPHARMACEUTICAL CO LTD
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