Carbapenem antibiotic containing sulfhydryl piperidine

A representative, methyl-based technology, applied in the field of medicine, can solve the problems of low clinical availability, increased bacterial resistance, and inability to meet clinical needs.

Active Publication Date: 2009-02-11
XUANZHU BIOPHARMACEUTICAL CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Due to the continuous increase of bacterial resistance due to the abuse of antibiotics and the limitation of digestive tract absorption, the currently marketed carbapenems can only be administered as injections in clinical practice, and the clinical utilization is not high. The half-life of tapenem is relatively short, which can no longer meet the clinical needs

Method used

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  • Carbapenem antibiotic containing sulfhydryl piperidine
  • Carbapenem antibiotic containing sulfhydryl piperidine
  • Carbapenem antibiotic containing sulfhydryl piperidine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0110] Example 1 Preparation of 1-tert-butoxycarbonyl-5-methanesulfonyloxypiperidine-2-methanol

[0111] In the dry reaction flask, add 100ml of dioxane, then add 6.8g (50mmol) of anhydrous zinc chloride, 5.4g (100mmol) of potassium borohydride, stir at room temperature for 1h, then add 1-tert-butoxycarbonyl-5- 8.4 g (25 mmol) of methyl methanesulfonyloxypiperidine-2-carboxylate. The temperature was slowly raised to reflux under stirring for 2h. Cool to room temperature, add 100ml of 1mol / L hydrochloric acid to dilute, and extract with ethyl acetate. The organic phase was washed with saturated brine, dried and concentrated to obtain 6.6 g of 1-tert-butoxycarbonyl-5-methanesulfonyloxypiperidine-2-methanol, yield: 85.3%.

Embodiment 2

[0112] Example 2 Preparation of 5-acetylthio-1-tert-butoxycarbonylpiperidine-2-methanol

[0113] In the dry reaction flask, add 15.5g (50mmol) of 1-tert-butoxycarbonyl-5-methanesulfonyloxypiperidine-2-methanol and 9.2g (100mmol) of potassium thioacetate, then add DMF150ml, stir and heat until dissolved Afterwards, heat preservation reaction 10h. After cooling to room temperature, dilute with 200ml of water, extract with ethyl acetate, wash the organic phase with water, dry and concentrate to obtain 13.4g of the product, yield: 92.5%.

Embodiment 3

[0114] Example 3 Preparation of 5-mercapto-2-[N-tert-butoxycarbonyl-N-(3-benzoic acid)amino]methylene-1-(tert-butoxycarbonyl)piperidine prepare

[0115] Under the protection of nitrogen, add 5.8g (20mmol) of 5-acetylthio-1-tert-butoxycarbonylpiperidine-2-methanol, 100ml of dichloromethane, drop into 4ml of TMSI (30mmol), stir vigorously at room temperature for 4h, ice Cool in a water bath to 0°C, stir for 30 minutes, and filter under reduced pressure. The filter cake was washed with a small amount of dichloromethane, and the filtrate was collected in a precooled flask. Under the protection of nitrogen at 0°C, a solution of 4.7g (21mmol) 3-tert-butoxycarbonylamino-benzoic acid in 20ml triethylamine / tetrahydrofuran (1:4, v / v) was added dropwise to the solution. , reacted at 0-5°C for 4h, decolorized the reaction solution, filtered it with suction, concentrated the filtrate to dryness under reduced pressure, then added 50ml of 5mol / L hydrochloric acid, stirred and reacted at...

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Abstract

The invention pertains to the technical field of medicine and particularly relates to carbon-substituted penem antibiotic which contains sulfhydryl piperidine and is shown as general formula (I), and pharmaceutically acceptable salts, easily hydrolysable ester and isomers of the antibiotic; wherein, R<1>, R<2>, R<3>, R<4>, R<5>, R<6> and R<7> are defined as the specification. The invention also relates to a preparation method of the compounds, medicine composition containing the compounds as well as application of the compounds to the preparation of medicines 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 carbapenem antibiotics containing mercaptopiperidine, pharmaceutically acceptable salts thereof, easily hydrolyzed esters thereof, isomers thereof, preparation methods of these compounds, and compounds 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] Carbapenem antibiotics are a class of β-lactam antibiotics developed in the 1970s. It has attracted much attention because of its broad antibacterial spectrum, strong antibacterial activity, and stability to β-lactamase. Its structural feature is that the sulfur at the 1-position of the penicillane core is replaced by carbon, and the 2-position has a double bond, which combines the five-membered ring of penicillin and the conjugated double bond of cephalosporin to...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D477/20A61K31/4439A61K31/407A61P31/00
CPCY02P20/55
Inventor 黄振华
Owner XUANZHU BIOPHARMACEUTICAL CO LTD
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