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

Piperazinone substituted tetracycline derivatives

A halogen and compound technology, applied in the direction of tetracycline active ingredients, organic chemistry, antibacterial drugs, etc., can solve the problems of unsatisfactory activity of Gram-negative bacteria, inconvenient medication, and pain of patients

Active Publication Date: 2010-03-31
HAINAN SIHUAN PHARMA
View PDF0 Cites 15 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Tigecycline has a broad antibacterial spectrum. It not only has the antibacterial activity of early tetracyclines, but also has antibacterial activity against pathogenic bacteria resistant to tetracyclines due to the efflux mechanism and ribosome protection mechanism. However, it has antibacterial activity against some Gram-negative bacteria. Activity is not ideal
Moreover, tigecycline can only be infused intravenously, and needs to be administered twice a day, which is inconvenient and brings pain to the patient

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
  • Piperazinone substituted tetracycline derivatives
  • Piperazinone substituted tetracycline derivatives
  • Piperazinone substituted tetracycline derivatives

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0114] Example 1 [S-(4α, 12aα)]-9-amino-4,7-bis(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3, 10,12,12a-tetrahydroxy -1,11-dioxo-2-tetracenecarboxamide preparation

[0115] Throw 22.8g (50mmol) [S-(4α,12aα)]-4,7-bis(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro in the reaction bottle -3,10,12,12a-Tetrahydroxy-1,11-dioxo-2-naphthalene carboxamide dihydrochloride, dissolved in 150ml of concentrated sulfuric acid, stirred and cooled in an ice bath, then added 6.8g sodium nitrate, and the mixture was stirred in an ice bath for 1 h. After the reaction was completed, the mixture was added dropwise to 2000ml of ether, and a solid was precipitated, which was washed with a small amount of ether and dried. Add the solid to 100ml of ethanol, then add 2g of 10% palladium carbon, and stir at room temperature under 2MPa hydrogen pressure for 1.5h. After filtration and concentration under reduced pressure, 800ml of ether was added to the residue under vigorous stirring. Filter and...

Embodiment 2

[0116] Example 2 Preparation of 4-tert-butylmorpholine-2,6-dione

[0117] 1. Preparation of 2,2'-[(tert-butyl)amino]diacetic acid

[0118] Add 4.7g (50mmol) of chloroacetic acid, 40ml of water, 5.6g (100mmol) of KOH, and 1.8g (25mmol) of tert-butylamine to the reaction flask, heat it in a water bath to 70°C, react for 4h and then cool it to room temperature. Neutralize, distill under reduced pressure, filter, adjust the pH value of the filtrate to about 3, and cool to obtain 3.5 g of the product, yield: 75.0%.

[0119] 2, Preparation of 4-tert-butylmorpholine-2,6-dione

[0120] Add 9.5g (50mmol) of 2,2'-[(tert-butyl)amino]diacetic acid and 20ml of acetic anhydride to the reaction flask, heat it in a water bath to 70°C, react for 24h and distill under reduced pressure to obtain 5.3g of the product, yield: 62%.

Embodiment 3

[0121] Example 3 [S-(4α, 12aα)]-9-[N-4-tert-butylpiperazine-2,6-dione-1-yl]-4,7-bis(dimethylamine base)-1,4,4a,5,5a,6,11,12a-octahydro-3,10,12,12a-tetrahydroxy-1,11-dioxo-2-tetracenecarboxamide (compound 9) of preparation

[0122] Add 100ml of toluene and 8.9g (52mmol) of 4-tert-butylmorpholine-2,6-dione into the dry reaction flask, stir and raise the temperature to above 80°C, slowly add [S-(4α, 12aα)] in batches -9-amino-4,7-bis(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,10,12,12a-tetrahydroxy-1,11 -Dioxo-2-tetracenecarboxamide 14.2g (30mmol), stirred at reflux for 4h. After the reaction is complete, cool to 60°C. Poured into crushed ice with vigorous stirring, a solid precipitated. After filtration, the filter cake was recrystallized with ethanol to obtain 12.7 g of the target compound, yield: 67.8%.

[0123] Molecular formula: C 31 h 39 N 5 o 9 Molecular weight: 625.67 Mass spectrum: (m / e): 626 (M+1)

[0124] Elemental analysis: Theoretical value: C, ...

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 medicament, and particularly relates to piperazinone substituted tetracycline derivatives shown in a general formula (I), and pharmaceutically acceptable salts or isomers thereof, wherein R<1a>, R<1b>, R<2>, R<3a>, R<3b>, R<4>, R<5a>, R<5b>, R<6>, R<7>, R<8>, R<9>, R<10>, R<11>, R<12>, R<13>, X and Y are defined in the specification. The invention also relates to a method for preparing the compounds, medicinal composition containing the compounds, as well as application of the compounds in the preparation of medicaments for treating and / or preventing tetracycline sensitive diseases, particularly in the preparation of medicaments for treating infectious diseases.

Description

1. Technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to tetracycline derivatives substituted by piperazinone, pharmaceutically acceptable salts or isomers thereof, preparation methods of these compounds, pharmaceutical compositions containing these compounds, and preparation of these compounds Use in medicines for treating and / or preventing tetracycline-sensitive diseases, especially in preparing medicines for treating infectious diseases. 2. Background technology [0002] Tetracycline antibiotics are a class of oral broad-spectrum antibiotics and semi-synthetic derivatives produced by the fermentation of the actinomycete Streptomyces, against Rickettsia, many Gram-positive bacteria and Gram-negative bacteria, lymphogranuloma venereum The pathogen, the inclusion body conjunctivitis pathogen and the psittacosis pathogen have good pharmacological effects. [0003] The first tetracycline antibiotic was aureomycin isolate...

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): C07D241/08C07D487/04C07D471/04C07D403/04C07D403/06A61K31/65A61P31/04
Inventor 黄振华张蕙周岩周广连
Owner HAINAN SIHUAN PHARMA
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