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

N-substituted amino phenyl-14 beta-(aminomethyl) triptodiolide derivative and preparation method and application thereof

A technology of triptolide and aminomethyl table, applied in the field of medicine, can solve the problems of large toxic and side effects, no fundamental change in the main structure, narrow treatment window and the like

Inactive Publication Date: 2013-11-13
SHANGHAI INST OF MATERIA MEDICA CHINESE ACAD OF SCI
View PDF3 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In addition to extensive research on anti-tumor effects, triptolide has also entered clinical trials for the treatment of leukemia. However, triptolide's relatively large toxic and side effects and too narrow therapeutic window limit its clinical application.
In the past, most of the structural modification of triptolide was limited to the introduction of water-soluble groups, and there was no fundamental change in the main structure

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
  • N-substituted amino phenyl-14 beta-(aminomethyl) triptodiolide derivative and preparation method and application thereof
  • N-substituted amino phenyl-14 beta-(aminomethyl) triptodiolide derivative and preparation method and application thereof
  • N-substituted amino phenyl-14 beta-(aminomethyl) triptodiolide derivative and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

preparation Embodiment 1

[0058] Preparation Example 1 compound (3)

[0059]

[0060] Under argon protection, 50 mL of anhydrous tetrahydrofuran was added into a reaction flask containing magnesium chips (900 mg, 37.5 mmol), and chloromethyldimethylisopropoxysilane (6 mL) was added dropwise to the reaction flask via a constant pressure dropping funnel. in the reaction system. After the addition, the dark gray reaction system was stirred at 50° C. for 30 min, and the Grignard reagent was prepared. The prepared Grignard reagent was added dropwise to triptolide ketone (LLDT-1) (3 g, 8.4 mmol) dissolved in 100 mL of dry THF. After reacting for 1.5 h at room temperature, the reaction was stopped. The reaction system was quenched with saturated ammonium chloride solution, extracted with ethyl acetate, the organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated to obtain the crude compound (2). Without further purification, compound (2) was dissolved in 50 mL ...

preparation Embodiment 2

[0062] Preparation Example 2 Compound (4)

[0063]

[0064] Compound 3 (420mg, 1.08mmol) was dissolved in 15mL of dichloromethane solvent, trichloroisocyanuric acid (376mg, 1.62mmol) was added at 0°C, followed by TEMPO (16mg, 0.108mmol) and quickly detected by TLC, the reaction Completely add sodium carbonate solution to quench the reaction and adjust the pH value to neutral, extract with dichloromethane, wash the organic phase with water and saturated brine respectively, dry over anhydrous sodium sulfate and concentrate, separate and purify by column chromatography to obtain compound 4 as a white solid (340 mg, 0.87 mmol, yield: 81%).

[0065] Compound 4: 1 H NMR (CDCl 3 , 300MHz) δ10.03(s, 1H), 4.76-4.59(m, 2H), 3.97(d, J=3.0Hz, 1H), 3.91(s, 1H), 3.75(d, J=5.9Hz, 1H ), 3.60(d, J=3.0Hz, 1H), 2.79-2.67(m, 1H), 2.38-2.26(m, 1H), 1.87(dd, J=14.7, 13.6Hz, 1H), 1.58(dd, J=12.6, 4.0Hz, 1H), 1.03(s, 3H), 0.83(d, J=6.9Hz, 3H), 0.79(d, J=6.9Hz, 3H); 13 C NMR (CDCl 3 , 100MHz)...

preparation Embodiment 3

[0066] Preparation Example 3 (14S)-14β-N-(2′-aminophenyl)-aminomethyl epitriptolide (LLDT-204)

[0067]

[0068] Compound 4 (39mg, 0.1mmol) was dissolved in 4mL of acetonitrile solvent, anthraniline (10.8mg, 0.1mmol) was added, stirred at room temperature for 0.5h, then sodium triacetoxyborohydride (42mg, 0.2mmol) was added, room temperature After 4 hours of reaction, the reaction was stopped, most of the solvent was distilled off under reduced pressure, the residue was diluted with water and extracted with ethyl acetate, the organic phase was washed with water and saturated brine respectively, dried over anhydrous sodium sulfate, concentrated, and separated by column chromatography. Purification gave white solid compound (14S)-14β-N-(2′-aminophenyl)-aminomethylepiptolide (LLDT-204) (38.4 mg, yield: 80%).

[0069] LLDT-204: 1 H NMR (300MHz, CDCl 3 )δ6.81-6.71(m, 4H), 4.66(m, 2H), 3.90-3.81(m, 3H), 3.49(d, J=3.0Hz, 1H), 3.38(d, J=9.6Hz, 1H ), 2.71(m, 1H), 2.49(sept, J=6.6...

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 provides a tripterygium diterpenoid lactone derivative shown in Formula II-6 or a pharmaceutically acceptable salt thereof, a preparation method thereof, a drug combination thereof and an application thereof in preparation of drugs for treatment of tumors, in particular to ovarian cancer or prostate cancer.

Description

technical field [0001] The invention relates to the field of medicine, in particular to a class of tripterygium wilfordii diterpenoid lactone derivatives and pharmaceutically acceptable salts thereof, their preparation methods and their use in the preparation of drugs for treating tumors, especially reproductive system tumors in the application. Background technique [0002] Tripterygium wilfordii, commonly known as Broken Heart Grass, is a woody vine of the genus Tripterygium genus Celastraceae, and is a plant with relatively abundant resources in my country. There are four kinds of Tripterygium plants, namely Tripterygium wilfordii Hook f., Tripterygium hypoglaucum Levl. Hutch, Tripterygium regelii Sprague et Takeda and Tripterygium regelii Sprague et Takeda. Rattan (Tripterygium forretii Dicls) is distributed in my country. Tripterygium wilfordii was first recorded in "Shenlong Materia Medica", and its main chemical components include diterpenes, triterpenes, sesquiterpe...

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): C07J73/00C07J75/00A61K31/585A61P35/00A61P35/02
Inventor 李援朝楼丽广周兵王蕾杨亚玺全海天冯慧瑾谢成英李征
Owner SHANGHAI INST OF MATERIA MEDICA CHINESE ACAD OF 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

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