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Semi-synthetic taxane derivative as well as preparation method and application thereof

A technology for taxanes and derivatives, applied in the field of semi-synthetic taxane derivatives and their preparation and application

Active Publication Date: 2015-05-13
CHANGZHI MEDICAL COLLEGE +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Recent activity studies have shown that its anticancer activity in vitro is significantly higher than that of paclitaxel and docetaxel, and the activity studies in vivo are also very exciting

Method used

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  • Semi-synthetic taxane derivative as well as preparation method and application thereof
  • Semi-synthetic taxane derivative as well as preparation method and application thereof
  • Semi-synthetic taxane derivative as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0052] Example 1 Preparation of compound II-1.

[0053]

[0054] Will 10-DAB (54.5g, 100.0mmol) was dissolved in dry tetrahydrofuran (1L), under argon protection, acetic anhydride (100.0mL, 1.0mol) and cerium trichloride heptahydrate (1.86g, 5.0mmol) were added under ice-cooling, slowly Return to room temperature, stir and react for 3 h, after the completion of the reaction as detected by thin-layer chromatography, the reaction solution was concentrated and evaporated to dryness, the resultant was diluted with ethyl acetate (1.5L), and distilled water (500mL×3) and saturated aqueous sodium chloride ( 500mL×3), washed with anhydrous sodium sulfate, concentrated to obtain a white solid crude product, and recrystallized to obtain 56.0g of white solid product II-1, with a yield of 96.0%.

[0055] 1 H NMR (600 MHz, CDCl 3 ) δ 8.10 (d, J = 7.2 Hz, 2H), 7.61 (t, J = 7.8 Hz, 1H), 7.48 (t, J =7.2 Hz, 2H), 6.32 (s, 1H), 5.62 (d, J = 7.2 Hz, 1H), 4.99 (d, J = 8.4 Hz, 1...

Embodiment 2

[0056] Example 2 Preparation of Compound III-1.

[0057]

[0058] Compound II-1 (51.5g, 88.0mmol) was dissolved in dry dichloromethane (1L), under argon protection, dry pyridine (200.0mL, 2.2mol) was added, the reaction solution was cooled to -35°C, and slowly Add trifluoromethanesulfonic anhydride (35.5mL, 220.0mmol) dropwise, control the dropwise addition within 1h, continue to stir for 4h, slowly return to room temperature and stir overnight, after the reaction is detected by thin layer chromatography, the reaction solution is dichloromethane (2.5L), washed successively with 1M aqueous sodium bisulfate solution (750mL×3), saturated aqueous sodium bicarbonate solution (300mL×3), saturated aqueous sodium chloride solution (300mL×3), dried over anhydrous sodium sulfate, and concentrated . The obtained orange-red solid crude product was dissolved in ethyl acetate / dichloromethane=1:2, petroleum ether was added until a large amount of solids were precipitated, left standing a...

Embodiment 3

[0060] Example 3 Preparation of compound IV-1.

[0061]

[0062] Compound III-1 (50.0g, 70.0mmol), sodium chloride (80.0g) and 4? molecular sieves (30.0g) were dissolved in dry acetonitrile / tetrahydrofuran=(1000mL / 100mL), under the protection of argon, prior to Stir at room temperature for 1 h, raise the temperature to 75°C and continue to stir for 2 h. After the reaction is detected by thin-layer chromatography, filter the reaction solution with suction, rinse the filter cake with a large amount of ethyl acetate, evaporate the filtrate to dryness, and wash with ethyl acetate (1.5 L ) was dissolved, washed successively with saturated aqueous sodium bicarbonate solution (300mL×3), saturated aqueous sodium chloride solution (300mL×3), dried over anhydrous sodium sulfate, concentrated, and subjected to column chromatography (dichloromethane / ethyl acetate=10 : 1) obtain white solid product IV-1 36.9g, yield 91.0%.

[0063] 1 H NMR (600 MHz, CDCl 3 ) δ 8.13 (d, J = 7.8 Hz...

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Abstract

The invention discloses a semi-synthetic taxane derivative. An anti-tumor effect test shows that the semi-synthetic taxane derivative has relatively good anti-tumor activity on a human lung adenocarcinoma cell line A549, a human breast cancer cell line MCF-7, a human glioblastoma cell line U251, a human pancreatic cancer cell line PANC-1, a human colon cancer cell line HCT116 and a human non-small lung cancer cell line H460. The semi-synthetic taxane derivative can be used for preparing anti-tumor drugs.

Description

technical field [0001] The present invention relates to a semi-synthetic taxane derivative, which is effective against human lung adenocarcinoma cell line A549, human breast cancer cell line MCF-7, human glioma cell line U251, human pancreatic cancer cell line PANC- 1. Both the human colon cancer cell line HCT116 and the human non-small cell lung cancer cell line H460 have good anti-tumor activity and can be used to prepare anti-tumor drugs. Background technique [0002] Paclitaxel and its semi-synthetic analog Docetaxel are the most effective anticancer drugs discovered by humans so far. It was first extracted from the bark of the Pacific yew (Taxus brevifolia, Taxus.brevifolia) The diterpenoids with unique anti-tumor activity have the characteristics of novel structure, unique anti-cancer mechanism, remarkable anti-cancer effect and broad anti-cancer spectrum. Approved for marketing, and as a first-line anticancer drug, it is widely used in breast cancer, lung cancer, gas...

Claims

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Application Information

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IPC IPC(8): C07D413/12A61P35/00
CPCC07D413/12
Inventor 李建伟张辉李安平李明花乔玉峰张涛
Owner CHANGZHI MEDICAL COLLEGE
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