Ursolic acid nitrogen heterocyclic ring structure modifiers with antitumor activity and preparation method for ursolic acid nitrogen heterocyclic ring structure modifiers

A technology of nitrogen-heterocycle and ursolic acid, applied in the field of ursolic acid nitrogen-containing heterocycle structure modification and its preparation

Inactive Publication Date: 2012-09-19
FUZHOU UNIV
View PDF5 Cites 7 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

There are no reports on the synthesis and anticancer activity of this kind of compounds at home and abroad.

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
  • Ursolic acid nitrogen heterocyclic ring structure modifiers with antitumor activity and preparation method for ursolic acid nitrogen heterocyclic ring structure modifiers
  • Ursolic acid nitrogen heterocyclic ring structure modifiers with antitumor activity and preparation method for ursolic acid nitrogen heterocyclic ring structure modifiers
  • Ursolic acid nitrogen heterocyclic ring structure modifiers with antitumor activity and preparation method for ursolic acid nitrogen heterocyclic ring structure modifiers

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0061] Preparation of 3-oxo-arbutane-12-ene-28-carboxylic acid (compound UA-2)

[0062] Preparation of PCC: In a 250mL three-neck flask, 50g CrO 3 Quickly add it to 92ml 6mol / L hydrochloric acid solution, and cool the homogeneous system in an ice bath after 5 minutes. After removing the ice bath, slowly drop 40 g of pyridine into the three-neck flask from the constant pressure funnel, and finish the dropping within at least 10 minutes. Cool the reaction system to 0 degrees Celsius again to obtain PCC as an orange-yellow solid. Filter it, dry it in vacuum for 2 hours, and seal it. refrigerated for later use;

[0063] Weigh 0.5g of UA, 0.7g of PCC, dissolve in 10mL of dichloromethane, stir at normal temperature and pressure, monitor the reaction process by TLC, end the reaction after 6-9 h, add water to stir and disperse, extract twice with chloroform, 25mL each time , Mix the organic phase, distill off the chloroform under reduced pressure, dissolve the residue with a little ...

Embodiment 2

[0069] Preparation of 3-oxo-arbutane-12-ene-28--acyl chloride

[0070] Dissolve 250mg of UA-2 in 10mL of ether, add 0.25mL of oxalyl chloride dropwise in batches, stir and react at room temperature for 24-36 h, evaporate the solvent and the gas generated by the reaction, add 10mL of cyclohexane to dissolve to obtain white foamy solid, the cyclohexane was recovered under reduced pressure to take out the unreacted net oxalyl chloride, and recovered 2-3 times to obtain the crude product of 3-oxoursolic acid chloride intermediate, which was set aside.

Embodiment 3

[0072] Preparation of 3-oxo-arbutane-12-ene-28--acyl-(1-ethyl)piperazine (compound UA-4a)

[0073] Take 125ml of N-ethylpiperazine, dissolve it in 15mL of dichloromethane, adjust the pH of the solution to 8-9 with the acid-binding agent triethylamine, add 30mg of DMAP (4-dimethylaminopyridine) as a catalyst, and add the above The dichloromethane solution of the fresh 3-oxoursolic acid chloride intermediate is stirred and reacted at room temperature, and the reaction process is monitored by TLC. After 12-24 h, the reaction is terminated, the reaction solvent is evaporated under reduced pressure, and the residual solid is dissolved in dichloromethane. Wash with 1% dilute HCl solution to remove excess piperazine and triethylamine and other basic impurities, wash twice, discard the water layer, mix the organic phase, evaporate dichloromethane under reduced pressure, and wash the residual solid with water , dry at 50°C. The dried product was purified by silica gel column chromatog...

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 the transformation of a chemical structure of a natural medicinal plant, namely ursolic acid, in particular to ursolic acid nitrogen heterocyclic ring structure modifiers with antitumor activity and a preparation method for the ursolic acid nitrogen heterocyclic ring structure modifiers. The ursolic acid nitrogen heterocyclic ring structure modifiers are ursolic acid nitrogen heterocyclic ring derivatives shown as a general formula (I). The preparation method comprises the following steps of: oxidizing or acetylating a C-3 hydroxyl group of the ursolic acid, performing condensation reaction of a C-17 carboxyl group and piperazine or a derivative of the piperazine so as to achieve the structural transformation of the ursolic acid, and thus obtaining a series of ursolic acid nitrogen heterocyclic ring structure modifiers. The in-vitro inhibitory activities of the ursolic acid nitrogen heterocyclic ring structure modifiers on human malignant melanoma A-375 cells, human gastric carcinoma AGS and BGC-823 cells are determined; and methyl thiazolyl tetrazolium (MTT) data show that the modifiers have a certain effect of inhibiting the proliferation of three kinds of cancer cells, and the inhibitory activity of partial compounds is even superior to that of paclitaxel.

Description

technical field [0001] The invention relates to a chemical structure transformation of natural medicinal plant ursolic acid, in particular to an ursolic acid nitrogen-containing heterocyclic structural modification with antitumor activity and a preparation method thereof. Background technique [0002] Ursolic acid (Ursolic acid, UA), also known as ursolic acid, ursolic acid, belongs to pentacyclic triterpenoids, chemical name (3β)-3-Hydroxyurs-12-en-28-oic acid, its relative molecular weight is 456.68, and the molecular formula is C 30 h 48 o 3 , which is widely distributed in nature in the form of free or glycosides. Pharmacological studies have found that ursolic acid has a wide range of biological effects, and ursolic acid has a variety of biological activities, such as anti-cancer, anti-HIV, anti-liver damage, anti-malarial, anti-inflammatory and antibacterial, etc., especially anti-cancer The activity is the most significant, and its anti-cancer spectrum is broad. 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 Applications(China)
IPC IPC(8): C07J63/00A61K31/58A61P35/00
Inventor 邵敬伟邹文滔
Owner FUZHOU UNIV
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap