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

Teniposide derivative, preparation method therefor and application of teniposide derivative

A technology of niposides and derivatives, applied in the field of teniposide derivatives and their preparation, and the preparation of anti-tumor drugs, which can solve the problems of toxic side effects, bioavailability, etc.

Pending Publication Date: 2020-07-28
汤亚杰
View PDF5 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, due to the disadvantages of strong toxic side effects and poor bioavailability, their clinical application is limited.

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
  • Teniposide derivative, preparation method therefor and application of teniposide derivative
  • Teniposide derivative, preparation method therefor and application of teniposide derivative
  • Teniposide derivative, preparation method therefor and application of teniposide derivative

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0048] Example 1 Synthesis and purification of 3″-(5-fluoro-benzothiazole-2-thio-acetate)-teniposide (compound 1)

[0049] (1) Synthesis of 3″-(5-fluoro-benzothiazole-2-thio-acetate)-teniposide

[0050] 1) 1.85g (10mmol) 5-F benzothiazole-2-mercapto, 3equiv. (equivalent) of anhydrous K 2 CO 3 Dissolve in THF, stir at room temperature for 10 min, add 1.8 equiv. of bromoacetic acid, and stir overnight. After the reaction, pour the reaction solution into a beaker filled with ice cubes, slowly add 1N HCl solution to adjust the pH to 4, extract with ethyl acetate, wash with 200mL saturated sodium bicarbonate and 200mL saturated sodium chloride, and collect the organic layer , evaporated to dryness under reduced pressure. A total of 2.22 g of the product was obtained, with a yield of 92%;

[0051] 2) 222 mg (1.5 mmol) of 5-fluoro-benzothiazole-2-thio-acetic acid, 656 mg (1 mmol) of teniposide, 1-ethyl-3 (3-dimethylpropylamine) carbodiimide EDCI Add 229mg (1.2mmol), 162mg (2mmol...

Embodiment 2

[0057] Example 2 Synthesis and purification of 3″-(5-fluoro-benzoxazole-2-thio-acetate)-teniposide (compound 2)

[0058] (1) Chemical synthesis of 3″-(5-fluoro-benzoxazole-2-thio-acetate)-teniposide

[0059] 1) 1.85g (10mmol) 5-F benzoxazole-2-mercapto, 3equiv. of anhydrous K 2 CO 3 Dissolve in THF, stir at room temperature for 10 min, add 1.8 equiv. of bromoacetic acid, and stir overnight. After the reaction, pour the reaction solution into a beaker filled with ice cubes, slowly add 1N HCl solution to adjust the pH to 4, extract with ethyl acetate, wash with 200mL saturated sodium bicarbonate and 200mL saturated sodium chloride, and collect the organic layer , evaporated to dryness under reduced pressure. A total of 2.22 g of the product was obtained, with a yield of 92%.

[0060] 2) 222 mg (1.5 mmol) of 5-fluoro-benzoxazole-2-thio-acetic acid, 656 mg (1 mmol) of teniposide, 1-ethyl-3 (3-dimethylpropylamine) carbodiimide Add 229mg (1.2mmol) of EDCI, 162mg (2mmol) of 1-hy...

Embodiment 3

[0065] Example 3 Synthesis and purification of 2″-(5-fluoro-benzothiazole-2-thio-acetate)-teniposide (3)

[0066] Synthetic method is consistent with embodiment 1, preparation liquid phase methanol: water=6: 4 flow rate 2.5mL / min separation and purification;

[0067] Compound 3: 2″-(5-fluoro-benzothiazole-2-thio-acetate)-teniposide, white powder, C 41 h 36 FNO 14 S 3

[0068] 1 H NMR (500MHz, DMSO-d 6 )δ8.26(s, 1H), 78.00-7.91(m, 1H), 7.84(dd, J=8.9, 4.8Hz, 1H), 7.61-7.48(m, 1H), 7.34(td, J=9.0, 2.6Hz, 1H), 7.19(d, J=2.8Hz, 1H), 7.03(dd, J=5.0, 3.5Hz, 1H), 6.99(s, 1H), 6.41(s, 1H), 6.10(s, 2H), 6.01(s, 1H), 5.91(d, J=23.9Hz, 2H), 5.75(s, 1H), 5.40(d, J=5.7Hz, 1H), 4.91(d, J=3.2Hz, 1H), 4.77(d, J=8.3Hz, 1H), 4.34(d, J=5.3Hz, 1H), 4.32-4.21(m, 3H), 4.06(d, J=14.9Hz, 1H), 3.92- 3.76(m, 2H), 3.68-3.46(m, 10H), 3.06(dd, J=14.2, 5.4Hz, 1H), 2.97-2.79(m, 1H). 13 C NMR (126MHz, DMSO-d 6 )δ174.83,166.75,148.38,148.18,147.57,146.58,140.65,135.14,133.14,130.55,128.79,126.87,12...

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 discloses a teniposide derivative, a synthesis method therefor and application of the teniposide derivative. The teniposide derivative represented by a formula (V) shown in the description. The anti-tumor activity of the teniposide derivative is improved remarkably and the toxic or side effects are lowered, is obtained through introducing a heteroaromatic compound with low toxicity such as 5-fluoro-benzothiazol-2-thiol or 5-fluoro-benzoxazol-2-thiol into 2' and 3' positions of a saccharide ring of teniposide by means of an ester bond or amide bond. Shown by in-vitro tumor cell activity inhibiting experiments, the toxic or side effects of the compound represented by the formula (V) disclosed by the invention are remarkably lowered compared with those of the teniposide on the basis that the anti-tumor activity of the compound is equivalent to that of the teniposide.

Description

technical field [0001] The invention belongs to the field of teniposide derivatives, in particular relates to teniposide derivatives and a preparation method thereof, and also relates to the use of the teniposide derivatives in the preparation of antitumor drugs. Background technique [0002] Teniposide is a semi-synthetic glycoside derivative of podophyllotoxin, its structure is as follows [0003] [0004] The above-mentioned compound is an antitumor drug developed by Bristol-Myers Squibb Company of the United States. It acts on DNA topoisomerase II to break the DNA of tumor cells to achieve the purpose of treating tumors. However, their clinical applications are limited due to strong toxic side effects and poor bioavailability. Contents of the invention [0005] The purpose of the present invention is to overcome the defects of the prior art, modify teniposide, and provide a class of teniposide derivatives with good anti-tumor activity and its preparation method and...

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): C07H17/04C07H1/00C07H1/06A61P35/00
CPCC07H17/04C07H1/00C07H1/06A61P35/00
Inventor 汤亚杰程洁赵巍
Owner 汤亚杰
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