Double targeting hepatic tumor drug as well as synthetic method and application thereof

A dual-targeting technology for liver tumors, applied in the field of targeted biopharmaceuticals, to achieve obvious therapeutic effects, slow down tumor progression, and reduce toxic and side effects

Inactive Publication Date: 2018-12-21
YANBIAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Aberrant regulation of cathepsin B leads to degradation of...

Method used

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  • Double targeting hepatic tumor drug as well as synthetic method and application thereof
  • Double targeting hepatic tumor drug as well as synthetic method and application thereof
  • Double targeting hepatic tumor drug as well as synthetic method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035] This embodiment provides a dual-target liver tumor drug, the chemical structural formula is as follows:

[0036]

[0037] Further, a method for synthesizing the dual-target liver tumor drug is provided, comprising the steps of:

[0038]

[0039] (1) Dissolve penta-O-acetyl-B-D-galactopyranose and 2-azidoethanol in 40ml of anhydrous dichloromethane, cool to -10°C under argon atmosphere, add boron trifluoride ether, The molar ratio of penta-O-acetyl-B-D-galactopyranose, 2-azidoethanol and boron trifluoride ether was 8.97:17.93:13.45, reacted for 24 hours, and then extracted three times with dichloromethane, saturated bicarbonate Wash once with sodium solution, once with saturated sodium chloride, dry the organic layer over anhydrous sodium sulfate, filter, concentrate, and column chromatography (developing solvent: n-hexane / ethyl acetate (v:v)=2 / 1, Rf=0.5 ), to obtain white viscous compound II.

[0040] (2) Dissolve compound II in step (1) with 20ml of methanol, t...

Embodiment 2

[0043] This embodiment provides a dual-target liver tumor drug, the chemical structural formula is as follows:

[0044]

[0045] Further, a method for synthesizing the dual-target liver tumor drug is provided, comprising the steps of:

[0046]

[0047] (1) Dissolve acetylgalactose and 2-azidoethanol in 5ml of anhydrous dichloromethane, cool to 5°C under an argon atmosphere, add boron trifluoride ether, acetylgalactose, 2-azidoethanol The molar ratio of boron trifluoride ether is 1.28:2.57:1.93, reacted for 24h, then extracted three times with dichloromethane, washed once with saturated sodium bicarbonate solution, washed once with saturated sodium chloride, and dried the organic layer with anhydrous sodium sulfate , filtered, concentrated, and column chromatographed (developing solvent: dichloromethane / ethyl acetate (v:v) = 1 / 1, Rf = 0.22) to obtain compound II in light yellow transparent viscous shape.

[0048] (2) Dissolve compound II in step (1) with 10ml of methanol...

Embodiment 3

[0051] This embodiment provides a dual-target liver tumor drug, the chemical structural formula is as follows:

[0052]

[0053] Further, a method for synthesizing the dual-target liver tumor drug is provided, comprising the steps of:

[0054]

[0055] (1) Dissolve acetylglucose and 2-azidoethanol in 5ml of anhydrous dichloromethane, cool to 0°C under an argon atmosphere, add boron trifluoride ether, acetylglucose, 2-azidoethanol and three The molar ratio of boron fluoride ether is 1.28:2.57:1.93, reacted for 24h, then extracted three times with dichloromethane, washed once with saturated sodium bicarbonate solution, washed once with saturated sodium chloride, dried the organic layer with anhydrous sodium sulfate, filtered , concentration, and column chromatography (developing solvent: dichloromethane / ethyl acetate (v:v) = 1 / 1, Rf = 0.27) to obtain compound II as a white powder.

[0056] (2) Dissolve the compound II in step (1) with 10ml of methanol, then add sodium met...

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Abstract

The invention relates to a double targeting hepatic tumor drug as well as a synthetic method and application thereof. The double targeting hepatic tumor drug has a terminal structure (galactose or N-acetyl galactose) capable of specifically binding to asialoglycoprotein receptor at the surface of a hepatocyte, and therefore the double targeting hepatic tumor drug is capable of binding to the asialoglycoprotein receptor so as to be brought into the interior of a hepatic tumor cell by means of the endocytosis of the hepatic tumor cell. On the other hand, experiments prove that the enzyme hydrolysis of the overexpressed cathepsin B in hepatic tumor cell lysosome is performed on the double targeting hepatic tumor drug to release Adriamycin, that is, active ingredients are released while the level of cathepsin B can be reduced, so as to slow down tumor progression. In summary, the double targeting hepatic tumor drug prepared by the invention uses asialoglycoprotein receptor and cathepsin Bas double target spots for having an effect, has obvious therapeutic effect, and meanwhile significantly reduces the toxic and side effects on other normal tissues and cells.

Description

technical field [0001] The invention belongs to the technical field of targeted biological drugs, and in particular relates to a dual-targeted liver tumor drug, a synthesis method and an application thereof. Background technique [0002] In 2015, China's cancer epidemiological statistics showed that the incidence and mortality of liver cancer in my country ranked third. Liver cancer is one of the common malignant tumors, which seriously threatens the life of our citizens. Due to the unique structure of the liver, patients have no obvious symptoms when early-stage lesions occur, and liver cancer cannot be diagnosed correctly in time. , and it is very difficult to cure patients with advanced liver cancer, so early detection and diagnosis of liver cancer and research and development of drugs for the treatment of advanced liver cancer are urgent problems to be solved. The asialoglycoprotein receptor (ASGPR) is a calcium-dependent carbohydrate-binding protein composed of the C-...

Claims

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Application Information

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IPC IPC(8): C07H15/04C07H1/00A61P35/00
CPCA61P35/00C07H1/00C07H15/04
Inventor 田熙哲罗竺荔金香梅
Owner YANBIAN UNIV
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