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

Preparation and anti-tumor application of 7-N3-brefeldin A and 1,2,3-triazole derivative thereof

A brefeldin and 7-N3- technology is applied in the fields of preparation and anti-tumor application of 7-N3-brefeldin A and its 1,2,3-triazole derivatives, and can Solve the problems of unsatisfactory, short plasma half-life, poor water solubility, etc.

Active Publication Date: 2015-05-06
ZHEJIANG UNIV OF TECH
View PDF6 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, due to its unsatisfactory pharmacokinetic properties (low bioavailability, poor water solubility, short plasma half-life, etc.), brefeldin A cannot be used as an anti-tumor therapeutic agent in clinical practice.

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
  • Preparation and anti-tumor application of 7-N3-brefeldin A and 1,2,3-triazole derivative thereof
  • Preparation and anti-tumor application of 7-N3-brefeldin A and 1,2,3-triazole derivative thereof
  • Preparation and anti-tumor application of 7-N3-brefeldin A and 1,2,3-triazole derivative thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0068] Embodiment 1: the preparation of 7-O-methylsulfonyl-BFA (formula IV)

[0069]

[0070] Under nitrogen protection, add 6 mL of pyridine to a 50 mL round bottom flask with a magnetic stirrer, then add BFA (500 mg, 1.79 mmol), then add triethylamine (240 mg, 2.38 mmol) and start stirring at -20 ° C; Methanesulfonyl chloride (273 mg, 2.38 mmol) was added dropwise to the mixture (dropwise for 10 min), and after the drop was completed, the mixture was reacted at -20°C for 2 h to terminate the reaction. After the reaction solution was concentrated, 30ml of ethyl acetate was added for dilution, washed with 5% citric acid solution (2×10ml), saturated sodium bicarbonate solution (2×10ml), saturated sodium chloride solution (2×10ml), and organic phase, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated to obtain a crude product, which was separated by thin-layer chromatography under the condition that the developer ethyl acetate (E):petroleum ether...

Embodiment 2

[0073] Example 2: 7-N 3 - Preparation of BFA (Formula II)

[0074]

[0075] Under the protection of helium, 10 mL of N, N-dimethylformamide was added to a 50 mL round bottom flask with a magnetic stirrer, and then compound IV 7-O-methylsulfonyl-BFA (400 mg, 1.12 mmol) was added, Then sodium azide (217mg, 3.35mmol) was added and stirred at reflux at 70°C for 4h to terminate the reaction. After the reaction solution was cooled and concentrated, 30ml of ethyl acetate was added to dilute, washed with 5% citric acid solution (2×10ml), saturated sodium bicarbonate solution (2×10ml), saturated sodium chloride solution (2×10ml), and combined The organic phase was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated to obtain a crude product. The crude product was separated by thin-layer chromatography under the condition of developing solvent E / P volume ratio = 1:5 to obtain compound II 7-N 3 - BFA (Rf = 0.3, yield 83.40%).

[0076] Compound Character...

Embodiment 3

[0084] Embodiment 3: the preparation of compound a-1

[0085]

[0086] Add THF:H to a 50 mL round bottom flask with a magnetic stir bar 2 O volume ratio=1:1 solvent (10ml), then add 30.5mg 7-N 3 - BFA (0.1 mmol), CuSO 4 .5H 2 O (0.01mmol, 2.5mg) and ascorbic acid (Vc0.015mmol, 2.64mg), start stirring; after stirring and dissolving, add alkyne III-A1 (R 1 =H, 0.15mmol, 19.8mg), stirred and reacted at room temperature for 6h, and the reaction process was detected and tracked by TLC. After the reaction was completed and cooled, the solvent was concentrated, and CH 2 Cl 2 Extract (3x20ml), combine the organic phases and wash with water, then add anhydrous MgSO 4 After drying, filtering and concentrating the filtrate, the obtained crude product was separated and purified by thin layer chromatography (E:P volume ratio=5:1) to obtain the corresponding product with a yield of 65.4%.

[0087] Compound Characterization:

[0088] Compound (a-1): Pale yellow solid. Yield 65.5%. ...

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 preparation and application of 7-N3-brefeldin A with anti-tumor activity and a 1,2,3-triazole compound of the 7-N3-brefeldin A. The compound provided by the invention has an efficient curative effect on liver cancer, lung cancer, breast cancer, renal cancer, colon cancer and prostatic cancer; the effective inhibition rate can be 80% through detection in vitro; and the method for obtaining the 7-N3-brefeldin A and the 1,2,3-triazole compound of the 7-N3-brefeldin A is simple and easy to operate. The chemical formula is as shown in the specification.

Description

(1) Technical field [0001] The present invention relates to a class of 7-N with antitumor activity 3 - Preparation and application of brefeldin A and its 1,2,3-triazole compounds. (2) Background technology [0002] Brefeldin A ((+) Brefeldin A, referred to as BFA) is a natural macrolide antibiotic and a secondary metabolite of Ascomycetes, also known as clinomycetes or ascodiosporum. In 1958, Singleton et al. first isolated it from the fermentation broth of Penicillium decumbens. In 1971, the complete configuration of BFA was determined by X-ray crystal structure analysis. Brefeldin A molecular formula C 16 h 24 o 4 , molecular weight 280Da, molecular structure contains 5 chiral centers, 2 double bonds, 1 five-membered carbon ring and 1 13-membered macrocyclic lactone, the structure is shown in formula I below: [0003] [0004] Brefeldin A has a variety of biological activities, including antifungal, antiviral, antinematode, antimitotic, and it has been found to ha...

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): C07D405/04C07D313/00C07K5/09A61K38/06A61K31/4192A61P35/00
CPCC07D313/00C07D405/04C07K5/0817
Inventor 朱勍张海峰郑裕国王亚军
Owner ZHEJIANG UNIV OF TECH
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