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

r 9 with r 10 Linked hydrophilic berberine derivatives and their application in the preparation of medicines

A dihalomethyl berberine and drug technology, applied in the field of 8-dihalomethyl berberine type quaternary ammonium salt compounds, can solve the problem of no significant improvement in drugability and toxicity, pharmacological action strength, chemical structure stability , poor solubility, etc.

Active Publication Date: 2021-03-30
INST OF MATERIA MEDICA CHINESE ACAD OF MEDICAL SCI
View PDF4 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0012] In summary, poor solubility is one of the main obstacles in the clinical application of imine-quaternized berberine-type quaternary ammonium compounds
The improvement of fat solubility helps to improve its pharmacological effects, but due to the problems of toxicity, strength of pharmacological effects, stability of chemical structure, etc., it has not significantly improved its druggability

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
  • r  <sub>9</sub> with r  <sub>10</sub> Linked hydrophilic berberine derivatives and their application in the preparation of medicines
  • r  <sub>9</sub> with r  <sub>10</sub> Linked hydrophilic berberine derivatives and their application in the preparation of medicines
  • r  <sub>9</sub> with r  <sub>10</sub> Linked hydrophilic berberine derivatives and their application in the preparation of medicines

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0106] The preparation process and structural identification data of the active compounds of the present invention, wherein the compound number corresponds to the specific compound number in the content of the present invention.

[0107] One, the preparation experiment example of compound of the present invention

experiment example (1

[0108] Experimental example (1) Preparation process and structure identification data of compound 1

[0109] Coptisine hydrochloride (2.0g, 5.62mmol) was dissolved in 200mL chloroform-methanol (3:1) mixed solvent in the reaction flask, added concentrated ammonia water 24ml, stirred and reacted at room temperature for 24h, then separated the chloroform layer, and The chloroform layer was washed twice with water and washed with anhydrous MgSO 4 After drying, it was filtered; the filtrate was evaporated to dryness, and the resulting crude product was purified by silica gel column chromatography, eluting with dichloromethane, and the eluate was concentrated to obtain 617 mg of 8-trichloromethyldihydrocoptisine as a light yellow solid, with a yield of 25.0%. 1 H NMR (500MHz, CDCl 3 )δ:2.63–2.78(m,1H,NCH 2 C H 2 ),3.35(m,1H, NCH 2 C H 2 ),3.71(m,1H,NC H 2 CH 2 ),3.78-3.90(m,1H,NC H 2 CH 2 ),5.42 (s,1H,CH-CCl 3 ),5.91(br,1H,OCH 2 O),5.95(br,2H,OCH 2 O),6.02(br,2H,OCH ...

experiment example (2

[0110] Experimental example (2) Preparation process and structure identification data of compound 3

[0111] Dissolve berberine hydrochloride (2.0g, 5.38mmol) in 60ml chloroform in a reaction flask, add 24ml of concentrated ammonia water, stir and react at room temperature for 24h, then separate the chloroform layer, wash the chloroform solution with water twice, and wash with Anhydrous MgSO 4 After drying the chloroform solution, filter it, and evaporate the filtrate to dryness to obtain a residue; the residue is separated and purified by silica gel column chromatography, eluted with dichloromethane, and the eluent is evaporated to dryness to obtain 8-trichloromethyldihydroberberis The base is 1.775 g of light yellow solid, the yield is 78.9%. 1 H NMR (500MHz, CDCl 3 )δ: 2.73 (d, J=15.5Hz, 1H, NCH 2 C H 2 ),3.33(m, 1H,NCH 2 C H 2 ),3.71(m,1H,NC H 2 CH 2 ),3.87(ov,4H,ArOCH 3 , NC H 2 CH 2 ),3.94(s,3H,ArOCH 3 ),5.65(s,1H,CH-CCl 3 ),5.94(s,2H,OCH 2 O),6.08(br s...

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

PropertyMeasurementUnit
control rateaaaaaaaaaa
Login to View More

Abstract

The invention discloses 8-dihalomethyl berberine type quaternary ammonium salt compounds represented by general formulas I and II, its synthesis method and its application in the preparation of medicines. Compared with the substrate, the 8-dihalomethyl berberine type compound shows more obvious hydrophilicity without conventional hydrophilic groups; the 8-dihalomethyl berberine-type compound is small Berine-type compounds have significant antimicrobial activity, anti-inflammatory activity, anti-ulcerative colitis activity and anti-tumor activity; they can be associated with tumorigenesis in colon cancer, liver cancer, lung cancer, breast cancer, osteosarcoma and glioma tumor cells Related target molecules show clear and significant regulatory effects and have significant anti-tumor activity. The pharmacological action intensity of the compound of the invention is higher than that of the control drug, and has the characteristics of no toxicity or low toxicity, and can be used to prepare drugs for preventing, alleviating and / or treating microbial infection, inflammation, ulcerative colitis and tumors.

Description

technical field [0001] The present invention relates to the 8-dihalomethyl berberine type with low toxicity or non-toxic hydrophilic imine type quaternized ammonium salt synthesized from naturally occurring berberine type alkaloid quaternary ammonium salt substrates Quaternary ammonium salt compound, preparation method of the compound of the present invention, anti-tumor, anti-microbial infection, anti-inflammatory and anti-ulcerative colitis pharmacological activities of the compound of the present invention. Compared with the natural berberine type alkaloid quaternary ammonium salt substrate, the compound of the present invention has obvious hydrophilicity. The pharmacological activity screening experiment carried out to the compound of the present invention proves that the 8-dihalomethyl berberine type quaternary ammonium salt compound of the imine type quaternary ammonium salt of the present invention has significant antitumor, antimicrobial infection, anti-inflammatory an...

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): C07D455/03A61K31/4375A61P31/04A61P31/10A61P29/00A61P1/00A61P35/00A61K8/49A61Q19/00A23L33/00
CPCC07D455/03A61P31/04A61P31/10A61P29/00A61P1/00A61P35/00A61K8/4926A61Q19/00A23L33/00A23V2002/00A23V2200/308A23V2200/30A23L33/10A61P1/04C07D493/14C07D493/22
Inventor 秦海林吴练秋李想张海婧宋利宋华琛邓安珺唐晓楠张志辉李志宏
Owner INST OF MATERIA MEDICA CHINESE ACAD OF MEDICAL SCI
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