Tetrandrine derivatives and preparation method thereof, and application of tetrandrine derivatives in preparing anti-tumor medicines

A technology for tetrandrine and derivatives is applied in the fields of tetrandrine derivatives and their preparation and application in the preparation of antitumor drugs, and can solve the problems of unsatisfactory therapeutic effect of liver cancer and the like, and achieves simple preparation method and improved performance. Proliferation inhibitory activity, high product purity effect

Active Publication Date: 2014-07-09
SHANDONG NORMAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Even so, most of the drugs currently used clinically in my country for the treatment of liver cancer are not satisfact

Method used

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  • Tetrandrine derivatives and preparation method thereof, and application of tetrandrine derivatives in preparing anti-tumor medicines
  • Tetrandrine derivatives and preparation method thereof, and application of tetrandrine derivatives in preparing anti-tumor medicines
  • Tetrandrine derivatives and preparation method thereof, and application of tetrandrine derivatives in preparing anti-tumor medicines

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036] Weigh 5.92g of bisbenzylisoquinoline (in general formula II, X=H), 2.50g of sodium 2-chloroacetate and 1.05g of potassium carbonate, add them into a 500mL three-necked flask, dissolve in 200mL of ethanol, stir and heat to reflux, and Insulate and react for 8 hours, evaporate the solvent under reduced pressure, cool down to room temperature, neutralize to neutral with 10% HCl, add 50mL of water and extract with chloroform for 3 times (60mL×3), extract with anhydrous Na 2 SO 4 After drying for 8 hours, TLC tracked the separation and purification process of the reaction and the product, recovered chloroform, and dried the solid at 60°C for 4 hours to obtain 2.84 g of a yellow powder product with a yield of 41.33% and a purity of 98.51% (HPLC). The melting point of the target product: 153-154°C, time-of-flight mass spectrum: M / e (326.1574), and the molecular formula is C 39 h 43 o 7 N 2 Cl, 13 C NMR (75MHz, DMSO-d 6 ): δ20.65(C-4), 23.24(C-4’), 35.67(C-15), 49.70(C-15...

Embodiment 2

[0038] Weigh 6.10g of 7-hydroxybisbenzylisoquinoline (in general formula II, X=OH), 10.00g of sodium 2-bromoacetate and 0.50g of potassium carbonate, dissolve them in 150mL of n-butanol, and add them to a 500mL three-necked flask , stirred and heated to boiling, and kept stirring for 4 hours, distilled off the solvent under reduced pressure, cooled to room temperature, neutralized to neutral with 5% HBr, added 50 mL of water and extracted 3 times with acetone (60 mL×3), traced the relationship between the reaction and the product by TLC Separation and purification process, extract with anhydrous Na 2 SO 4 After drying for 8 hours, acetone was recovered, and the solid was dried at 60°C for 4 hours to obtain 3.54 g of a yellow powder product with a yield of 47.35% and a purity of 97.23% (HPLC). The melting point of the target product: 152-153°C, time-of-flight mass spectrum: M / e (334.1548), and the molecular formula is C 39 h 43 o 8 N 2 Br, 13 CNMR shows a carbonyl peak at...

Embodiment 3

[0040] Weigh 6.26g of 7-chlorobisbenzylisoquinoline (in general formula II, X=Cl), 3.00g of sodium 2-chloroacetate, and 1.20g of anhydrous sodium carbonate, dissolve them in 100mL of water, add them to a 500mL three-necked flask, Stir and freeze to 5°C, keep warm and stir to react for 24 hours, after rising to room temperature, neutralize with 10% HCl to neutral, distill out water under reduced pressure until the liquid volume is reduced to half, crystallize at room temperature for 8 hours, filter, and track the separation of reaction and product by TLC During the purification process, the obtained solid was dried at 60°C for 4 hours to obtain 2.75 g of a yellow powder product with a yield of 38.11% and a purity of 96.55% (HPLC). The melting point of the target product: 162-163°C, time-of-flight mass spectrum: M / e (343.1379), and the molecular formula is C 39 h 42 o 7 N 2 Cl 2 , 13 CNMR showed a carbonyl peak at δ=167.04, X-ray single crystal diffraction, namely compound ...

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Abstract

The invention discloses tetrandrine derivatives and a preparation method thereof. The structural general formula of the compounds is as shown in the specification. The method comprises the following steps: dissolving bisbenzylisoquinoline compounds used as raw materials in a certain solvent, adding a reactant Y, mixing, reacting for 0.1-72 hours at a temperature ranging from minus 20 to 300 DEG C and under a neutral or alkaline condition, adding an acid to a solution obtained after reacting and neutralizing, and then carrying out separation and purification to obtain target products. The tetrandrine derivatives prepared by the method have an outstanding inhibition effect on the proliferation of the human hepatocarcinoma cell line HepG2 and the human colon cancer cells HT29, and thus can be applied to preparing anti-tumor medicines.

Description

technical field [0001] The invention relates to a novel tetrandrine derivative, its preparation method and its application in the preparation of antitumor drugs. Background technique [0002] Tetrandrine, also known as Tetrandrine or Tetrandrine, is a bisbenzylisoquinoline compound. It is mainly used clinically for rheumatic pain, arthralgia, neuralgia, and also for silicosis. Hanjisong (dimethyl iodide tetrandrine, the quaternary ammonium salt of tetrandrine) is a striated muscle relaxant, which can be used clinically to relax striated muscles during surgery. Experimental studies have proved that tetrandrine has certain effects on lung cancer, chronic myelogenous leukemia, liver cancer, neuroblastoma, breast cancer, etc., and its mechanism is related to the reversal of multidrug resistance, induction of apoptosis, radiosensitization, Inhibition of tumor angiogenesis. It has been proved by in vitro experiments (Xu Meng, et al. Experimental study on the reversal of chemothe...

Claims

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Application Information

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IPC IPC(8): C07D491/18A61K31/4748A61P35/00
CPCC07D491/18
Inventor 刘玉法张萌毛霏霏陈冬梅张金娥
Owner SHANDONG NORMAL UNIV
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