Supercharge Your Innovation With Domain-Expert AI Agents!

Limonin oxime ether derivative, its preparation method and medical application

A use and pharmaceutical technology, applied in the fields of water-soluble limonin and deoxylimonin oxime ether derivatives, anti-inflammatory effects, and analgesia, can solve the problems of low oral bioavailability and limited clinical application, and achieve good Analgesic and pain relief effects

Active Publication Date: 2015-10-28
CHINA PHARM UNIV
View PDF3 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Limonin is easily soluble in fat-soluble organic solvents, and has high solubility in methanol and ethanol, but it is almost insoluble in water, and its oral bioavailability is extremely low, which limits its clinical application

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
  • Limonin oxime ether derivative, its preparation method and medical application
  • Limonin oxime ether derivative, its preparation method and medical application
  • Limonin oxime ether derivative, its preparation method and medical application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0058] Preparation of Compound IV

[0059] Add 1.0g (0.002mol) of limonin (III), 1.1g (0.016mol) of hydroxylamine hydrochloride, 45ml of absolute ethanol, and 15ml of pyridine into a 100ml eggplant-shaped bottle, and heat to reflux for 2.5h. Thin-layer chromatography (TLC) detection, after the reaction is complete, the reaction solution is cooled to room temperature, poured into 125ml of 5% dilute hydrochloric acid prepared in advance, adjusted to acidic pH, and cooled with ice water. The aqueous layer was extracted three times with 50 ml of dichloromethane, the combined extracts were washed three times with saturated brine, and dried over anhydrous sodium sulfate. Filter and distill off the solvent under reduced pressure. The crude product was subjected to column chromatography with dichloromethane:methanol (125:1) to obtain 0.98 g of a white solid with a yield of 95%. mp>250℃; 1 HNMR (CDCl 3 ,500MHz),δ(ppm):7.70(1H,brs),7.39(2H,d,J=1.7Hz),6.34(1H,s),5.46(1H,s),4.68(1H,d,...

Embodiment 2

[0061] Preparation of Compound I-1

[0062] Completely dissolve 0.50 g (0.001 mol) of IV in 25 ml of anhydrous tetrahydrofuran in a 50 ml eggplant-shaped bottle. Now add 0.2g (0.005mol) of 60% sodium hydride, stir at room temperature for 30min, add 0.55g (0.003mol) of 1-(2-chloroethyl) piperidine hydrochloride, potassium iodide 0.17 (0.001mol) and catalytic amount of TBAB, after continuing to stir at room temperature for 1 h, the temperature was raised to 80° C. for 12 h. It was detected by TLC that the reaction was complete, cooled, and the solvent was evaporated under reduced pressure. Add 100ml of water to the residue, adjust the pH to acidic with 5% dilute hydrochloric acid, extract the aqueous layer three times with 70ml of dichloromethane, combine the extracts, wash with saturated brine three times, and dry over anhydrous sodium sulfate. Filter and distill off the solvent under reduced pressure. The crude product was subjected to column chromatography with dichloromet...

Embodiment 3

[0065] Preparation of Compound I-2

[0066] Using compound IV and 1-(2-chloroethyl)morpholine hydrochloride as raw materials, the operation is the same as that of I-1, and the crude product is chromatographed with dichloromethane:methanol (75:1) to obtain I-2 white Solid 0.29g, yield 48%. mp138~141℃;IR(KBr,υcm -1 ):2963,1750,1025,807; 1 H NMR (CDCl 3 ,500MHz),δ(ppm):7.41(2H,d,J=4.6Hz),6.36(1H,s),5.49(1H,s),4.66(1H,d,J=13.0Hz),4.33(1H ,d,J=13.0Hz),3.96(1H,brs),3.86(4H,brs),3.80(1H,s),3.45(1H,dd,J 1 =2.9Hz,J 2 =14.0Hz),2.95(1H,dd,J 1 =3.8Hz,J 2 =16.8Hz), 2.67–2.93(4H,brs), 2.66(1H,dd,J 1 =1.9Hz,J 2 =16.7Hz),2.39(1H,d,J=11.6Hz),1.73-2.06(9H,m),1.49-1.53(2H,m),1.30(3H,s),1.25(3H,s),1.17 (3H,s),0.97(3H,s); 13 C NMR (CDCl 3 ,300MHz),δ(ppm):169.37,166.96,158.44,143.20,140.98,120.14,109.69,80.35,79.27,78.28,71.86,66.88,65.76,64.73,60.65,5546,54.247,46.9 ,37.99,35.84,33.09,30.27,21.59,21.34,19.78,19.57,17.99;HR-ESIMS m / z599.2958[M+H] + (calcd for C 32 h 43 N 2 o 9 ,59...

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 present invention relates to the field of medicinal chemistry, and in particular relates to limonin oxime ether derivatives (I) and (II), and the preparation method and the medicinal thereof. The pharmacological experiments show that the compounds of the present invention have analgesic and anti-inflammatory effects, and can be clinically used for alleviating pain and inflammatory diseases.

Description

technical field [0001] The invention relates to the field of medicinal chemistry, in particular to a class of water-soluble limonin and deoxylimonin oxime ether derivatives, their preparation methods, and their analgesic and anti-inflammatory effects. Background technique [0002] Statistics show that about 5.5 million people around the world suffer from cancer pain every day, and there are at least 100 million pain patients in my country. Pain, the most primitive suffering of human beings, has become a common concern of the global pharmaceutical industry. Various analgesics have been introduced one after another. On the other hand, the side effects caused by the abuse of analgesics also seriously endanger people's health. [0003] Limonoid analogues are highly oxidized tetracyclic triterpenoids from the Rutaceae and Meliaceae plant families, widely found in citrus plants. So far, more than 300 kinds of limonoid analogues have been separated, and limonin is the representati...

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): C07J73/00A61K31/585A61P29/00
CPCA61P29/00C07J73/008
Inventor 徐云根杨芸朱启华王欣慧龚国清杨俐嫣
Owner CHINA PHARM UNIV
Features
  • R&D
  • Intellectual Property
  • Life Sciences
  • Materials
  • Tech Scout
Why Patsnap Eureka
  • Unparalleled Data Quality
  • Higher Quality Content
  • 60% Fewer Hallucinations
Social media
Patsnap Eureka Blog
Learn More

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2025 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com