Azido-β-lactam small molecule probe based on tubulin and its preparation method and application

A small molecule probe, tubulin technology, applied in the application field of antitumor drug lead compounds and small molecule probes, can solve the problems of high price, cumbersome route, unfavorable large-scale production, etc., and achieves low cost and short route. , the effect of inhibiting development

Inactive Publication Date: 2019-08-09
河南省诚建检验检测技术股份有限公司
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  • Abstract
  • Description
  • Claims
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Problems solved by technology

[0007] It can be found that this method requires seven steps to synthesize the azide-containing tubulin small molecule probe, and the route is cumbersome.
At the same time, paclitaxel needs to be used as a raw material, which is expensive and unfavorable for large-scale production
[0008] This type of small molecule probe is of great significance to the study of the biological function of tubulin, and has not been reported in the literature so far

Method used

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  • Azido-β-lactam small molecule probe based on tubulin and its preparation method and application
  • Azido-β-lactam small molecule probe based on tubulin and its preparation method and application
  • Azido-β-lactam small molecule probe based on tubulin and its preparation method and application

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Embodiment Construction

[0024] In order to better illustrate the present invention, special examples are as follows:

[0025] Preparation of Example Compound (I-9)

[0026] 100ml 2M H 2 SO 4 Add 39g of 3-aminobenzyl alcohol or 4-aminobenzyl alcohol, 42g of sodium nitrite, and 42g of sodium azide to the solution, stir and react at 0°C, and filter with suction to obtain compound I-A. Take 15g of compound I-A, dissolve it in 150ml of dichloromethane, add 22g of pyridinium chlorochromate, stir at room temperature for 3h, extract and concentrate, and recrystallize from 10ml of ethanol to obtain compound I-B. Take 2.9g of compound I-B, add 3.6g of 3,4,5-trimethoxyaniline, stir at room temperature and filter with suction to obtain compound I-C. 0.03 mol of triethylamine, 0.02 mol of aromatic ring acetyl chloride, and 0.02 mol of compound I-C were added to 20 ml of anhydrous dichloromethane, and refluxed to obtain azide-β-lactam derivatives I-1 to I-9.

[0027] The structures of compounds (I-1~I-9) are c...

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Abstract

The invention discloses a tubulin-based nitrine-beta-lactam micromolecule probe and a preparation method and application and belongs to the field of medicinal chemistry. A beta-lactam mother nucleus is combined with nitrine active unit, so that simplicity and high efficiency are realized. The probe has a structural general formula as follows. Molecular in-vitro anti-cancer activity experiments of the probe show that the probe has certain inhibition effect on various tumor cells MCF-7, MGC-803 and A549. Especailly, activity of nitrine-beta-lactam probe molecule I-9 to MGC-803 cells is 85nM. On the other side, the compound can be combined with tubulin to inhibit tubulin polymerization and can serve as a potential tubulin micromolecule probe. By the probe, the problem that nitrine-type tubulin probes are few in type, troublesome to synthesize and high in cost is solved, and development of drug for inhibiting tubulin polymerization is facilitated.

Description

technical field [0001] The invention relates to the field of medicinal chemistry, in particular to a class of tubulin-based azido-β-lactam compounds, their preparation method and their application as a class of new anti-tumor drug lead compounds and small molecule probes. Background technique [0002] The photoaffinity labeling technology is mainly to form a specific and irreversible combination between the ligand and the binding site of the macromolecule after irradiation with light. The characteristics of this complex were further analyzed to characterize the receptor protein. At present, the most ideal photoaffinity markers are aromatic azides (Nature, 1969, 224, 511-512). [0003] The structure of the azide-containing tubulin small molecule probes reported so far is: [0004] [0005] The compound can bind to tubulin and inhibit the polymerization of tubulin. The synthesis method is as follows: [0006] [0007] It can be found that this method requires seven s...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D205/08C07D409/04A61P35/00G01N33/68
CPCC07D205/08C07D409/04G01N33/68
Inventor 张雁冰付冬君刘英超宋健毛若望杨佳佳赵若含张赛扬刘宏民
Owner 河南省诚建检验检测技术股份有限公司
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