Check patentability & draft patents in minutes with Patsnap Eureka AI!

Paclitaxel, Docetaxel Derivatives and Compositions and Their Antitumor Applications

A compound and pharmaceutical technology, applied in paclitaxel, docetaxel derivatives and compositions and their antitumor application fields

Active Publication Date: 2019-02-01
INST OF MATERIA MEDICA CHINESE ACAD OF MEDICAL SCI
View PDF7 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Patent WO9638138 (Protaxol, novel toxoids, Biophysica Foundation), WO9858927 (Buck Norton Pharmaceutical Co., Ltd.), CN00115426.5 (polyhydroxyl water-soluble derivatives of paclitaxel and its preparation method, Fudan University) disclose several novel soluble paclitaxel Derivatives can be used to treat tumors or other paclitaxel-sensitive diseases, but such new compounds that add water-soluble additional groups to paclitaxel molecules have not been developed into clinical drugs so far

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
  • Paclitaxel, Docetaxel Derivatives and Compositions and Their Antitumor Applications
  • Paclitaxel, Docetaxel Derivatives and Compositions and Their Antitumor Applications
  • Paclitaxel, Docetaxel Derivatives and Compositions and Their Antitumor Applications

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0104] Example 1 Preparation of 13-[(2'R,3'S)-3'-phenyl-2'-hydroxy-3'-(thiophene-2-methyl)amino-propionyl]-10-deacetyl- Baccatin III (Ia, R 1 =H,R 2 = Thiophen-2-yl, R 3 =Ph)

[0105]

[0106] step 1

[0107] Add compound III 211mg (0.2mmol), camphorsulfonic acid 19mg (0.08mmol), thiophene-2-carbaldehyde 90mg (0.8mmol) and molecular sieve 100mg in dry reaction bottle, seal, exchange argon and protect with argon balloon, finally add 3mL without Water and dichloromethane were reacted for 4 hours under stirring at room temperature. 10 mg (0.16 mmol) of sodium cyanoborohydride was added, and the reaction was continued for 1 hour, and the starting point disappeared as detected by TLC. The reaction solution was filtered, and the filtrate was washed successively with saturated sodium bicarbonate and saturated brine, and dried over anhydrous sodium sulfate. It was filtered, concentrated, and separated by silica gel column (petroleum ether: acetone = 5:1) to obtain 135 mg of w...

Embodiment 2

[0111] Example 2 Preparation of 13-[(2'R,3'S)-3'-phenyl-2'-hydroxy-3'-(thiophene-3-methyl)amino-propionyl]-10-deacetyl- Baccatin III (Ib, R 1 =H,R 2 = Thiophen-3-yl, R 3 =Ph)

[0112]

[0113] step 1

[0114] Add compound III 400mg (0.378mmol), camphorsulfonic acid 35mg (0.15mmol), thiophene-3-carboxaldehyde 102mg (0.9mmol) and molecular sieve 100mg in dry reaction bottle, seal, exchange argon and protect with argon balloon, finally add 4mL without Water and dichloromethane were reacted for 4 hours under stirring at room temperature. 19 mg (0.30 mmol) of sodium cyanoborohydride was added, and the reaction was continued for 1 hour, and the starting point disappeared as detected by TLC. The reaction solution was filtered, and the filtrate was washed successively with saturated sodium bicarbonate and saturated brine, and dried over anhydrous sodium sulfate. It was filtered, concentrated, and separated by a silica gel column (petroleum ether: acetone = 5:1) to obtain 184 ...

Embodiment 3

[0118] Example 3 Preparation of 13-[(2'R,3'S)-3'-phenyl-2'-hydroxy-3'-(thiazole-4-methyl)amino-propionyl]-10-deacetyl- Baccatin III (Ic, R 1 =H,R 2 = Thiazol-4-yl, R 3 =Ph)

[0119]

[0120] step 1

[0121] Add 500 mg (0.47 mmol) of compound III, 45 mg (0.19 mmol) of camphorsulfonic acid, 130 mg (1.15 mmol) of thiazole-4-carbaldehyde and 100 mg of molecular sieve into a dry reaction bottle, seal it, exchange argon and protect it with an argon balloon, and finally add 5 mL of Water and dichloromethane were reacted for 4 hours under stirring at room temperature. 25 mg (0.4 mmol) of sodium cyanoborohydride was added, and the reaction was continued for 1 hour, and the starting point disappeared as detected by TLC. The reaction solution was filtered, and the filtrate was washed successively with saturated sodium bicarbonate and saturated brine, and dried over anhydrous sodium sulfate. It was filtered, concentrated, and separated by a silica gel column (petroleum ether: ace...

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 derivatives of taxol and taxotere and a composition and anti-tumor application of the derivatives. Specifically, the invention discloses semi-synthetic taxol derivatives shown in a general formula (A) and pharmaceutically acceptable salts of the derivatives. The preparation method of the compounds comprises two steps; a preferable reducing agent used in the step 1 is sodium cyanoborohydride; a preferable Troc removal protecting group is treated with ammonium chloride and zinc powder. The invention further discloses a medicine composition; the medicine composition comprises an effective dosage of the compounds shown in the general formula (A) or pharmaceutically acceptable salts of the compounds and pharmacodynamically acceptable carriers. The invention also discloses the application of the compounds and the pharmaceutically acceptable salts of the compounds in preparation of anti-tumor medicines (The formula (A) is shown in the specification).

Description

technical field [0001] The present invention relates to a new class of paclitaxel derivatives and salts, a preparation method thereof, a pharmaceutical composition containing the compound, and an application of the compound in preparing medicine for treating cancer. Background technique [0002] Paclitaxel is a natural product isolated from Taxus brevifolia (Wani MC, Taylor HL, Wall ME, The isolation and structure of taxol, a novel antileukemic and antitumor agent from tausbrevifolia, J.Am.Chem.Soc. 1971, 93, 2325). The compound can promote microtubule polymerization and prevent its depolymerization in cells (Horwitz SB, Fant J, Schiff PB, Promotion of microtubule assembly in vitro by taxol, Nature, 1979, 277, 665), thereby blocking the process of cell mitosis, with strong cytotoxic and antitumor effects. Subsequent in-depth research on it also found that it has a broad anti-tumor spectrum, and it has been approved for marketing in many countries around the world for the t...

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): C07D409/12C07D417/12C07D409/14A61K31/381A61K31/427A61P35/00
CPCY02P20/55
Inventor 吴克美叶仙蓉俞晓明陈晓光王凤李永强李燕周玉美梅梅李云峰籍秀娟张福荣
Owner INST OF MATERIA MEDICA CHINESE ACAD OF MEDICAL SCI
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