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A semi-synthetic taxane derivative and its preparation method and application

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

Active Publication Date: 2019-03-01
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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  • A semi-synthetic taxane derivative and its preparation method and application
  • A semi-synthetic taxane derivative and its preparation method and application
  • A semi-synthetic taxane derivative and its preparation method and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

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

[0053]

[0054] 10-DAB (54.5 g, 100.0 mmol) was dissolved in dry tetrahydrofuran (1 L), under argon protection, acetic anhydride (100.0 mL, 1.0 mol) and cerium trichloride heptahydrate (1.86 g, 5.0 mol) were added under ice bath. mmol), slowly returned to room temperature, stirred and reacted for 3 h. After the reaction was detected by thin layer chromatography, the reaction solution was concentrated and evaporated to dryness. The resultant was diluted with ethyl acetate (1.5 L), followed by distilled water (500 mL×3), saturated chlorine Washed with an aqueous sodium chloride solution (500 mL×3), dried over anhydrous sodium sulfate, and concentrated to obtain a white solid crude product, which was recrystallized to obtain 56.0 g of a 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 = 7.8Hz, 1H), 7.48 (t, J =7.2 Hz, 2H), 6.32 (s, 1H), 5.62 (d, ...

Embodiment 2

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

[0057]

[0058] Compound II-1 (51.5 g, 88.0 mmol) was dissolved in dry dichloromethane (1 L), under argon protection, dry pyridine (200.0 mL, 2.2 mol) was added, the reaction solution was cooled to -35 °C, slowly Trifluoromethanesulfonic anhydride (35.5 mL, 220.0 mmol) was added dropwise, and the addition was completed within 1 h, continued stirring for 4 h, slowly returned to room temperature and stirred overnight. After the reaction was detected by thin layer chromatography, the reaction solution was diluted with dichloromethane (2.5L) diluted, washed with 1M aqueous sodium hydrogen sulfate solution (750 mL×3), saturated aqueous sodium hydrogen carbonate solution (300 mL×3), and saturated aqueous sodium chloride solution (300 mL×3) successively, dried over anhydrous sodium sulfate, concentrated . The obtained orange-red solid crude product was dissolved in ethyl acetate / dichloromethane=1:2, and petroleum ether was added u...

Embodiment 3

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

[0061]

[0062] Compound III-1 (50.0g, 70.0mmol), sodium chloride (80.0g) and 4Å molecular sieve (30.0g) were dissolved in dry acetonitrile / tetrahydrofuran=(1000mL / 100mL), under argon protection, before room temperature After stirring for 1 h, the temperature was raised to 75°C and the reaction was continued for 2 h. After the reaction was detected by thin layer chromatography, the reaction solution was suction filtered, the filter cake was rinsed with a large amount of ethyl acetate, the filtrate was evaporated to dryness, and ethyl acetate (1.5 L) Dissolved, washed with saturated aqueous sodium bicarbonate solution (300 mL×3) and saturated aqueous sodium chloride solution (300 mL×3) successively, dried over anhydrous sodium sulfate, concentrated, and subjected to column chromatography (dichloromethane / ethyl acetate=10: 1) 36.9 g of white solid product IV-1 was obtained, with a yield of 91.0%.

[0063] 1 H NMR (600 MHz, CD...

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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 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, and human pancreatic cancer cell line PANC- 1. Human colon cancer cell line HCT116 and human non-small cell lung cancer cell line H460 have good antitumor activity and can be used to prepare antitumor drugs. Background technique [0002] Paclitaxel (Paclitaxel) and its semi-synthetic analog Docetaxel (Docetaxel) are the most effective anticancer drugs discovered by humans so far. The resulting diterpenoids with unique anti-tumor activity have the characteristics of novel structure, unique anti-cancer mechanism, significant 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, gastric cancer, esophageal cancer, ovarian cancer, etc. The anticancer effect ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
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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