Hydroxamic acid micromolecule organic compound with thaizolidinone structure as well as derivatives, application and preparation method of hydroxamic acid micromolecule organic compounds

A technology of organic compounds and thiazolinones, applied in the field of medicine, can solve the problems of loss of activity of tumor suppressor genes and high activation of proto-oncogenes

Active Publication Date: 2015-03-25
EAST CHINA NORMAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Gene mutations, deletions, and chromosomal abnormalities usually result in loss

Method used

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  • Hydroxamic acid micromolecule organic compound with thaizolidinone structure as well as derivatives, application and preparation method of hydroxamic acid micromolecule organic compounds
  • Hydroxamic acid micromolecule organic compound with thaizolidinone structure as well as derivatives, application and preparation method of hydroxamic acid micromolecule organic compounds
  • Hydroxamic acid micromolecule organic compound with thaizolidinone structure as well as derivatives, application and preparation method of hydroxamic acid micromolecule organic compounds

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0061]

Embodiment 1-1

[0062] Example 1-1, Preparation of Compound 4-{2-[2-(3-bromophenyl)-4-carbonyl-3-thiazolyl]phenoxy}-N-hydroxybutyramide (FF001)

[0063] Take 2-aminophenol (1.90g, 10mmol) in toluene (30ml), cool the reaction system with an ice-water bath, add m-bromobenzaldehyde (1.16ml, 10mmol), react at 0°C for 20min, then heat the oil bath to 140°C The water was separated at reflux for 5h, and another reactant, thioglycolic acid (1.39ml, 20mmol), was added. Continue to reflux at 140°C to separate water for 5 hours, remove most of the solvent under reduced pressure, pass through a silica gel column after conventional treatment, and obtain compound I (2.59 g, 74%).

[0064] Compound I (400mg, 1.14mmol) was dissolved in N,N-dimethylformamide (8ml), potassium carbonate (787mg, 2.28mmol) and ethyl bromobutyrate (412mg, 2.28mmol) were added, heated to 50 After reacting at ℃ for about 3 hours, Intermediate II (466 mg, 91%) was isolated.

[0065] Add KOH (2.89g, 51.5mmol) to a solution of hydrox...

Embodiment 2

[0071] Example 2. Inhibitory effect of compounds of the present invention on HDACs enzyme activity at the molecular level.

[0072] We first screened the designed and synthesized compounds with novel structures for HDACs enzyme activity using the HDAC enzyme activity screening kit. During the experiment, the compound to be identified was incubated with HDAC active (HeLa or MDA-MB231 cell lysate) and HDAC colorimetric substrate (containing an acetylated lysine side chain. If the substrate is deacetylated, it will be After activation, a luminescent group is generated under the action of lysine chromogen. The final luminescent group is read and analyzed by a microplate reader.

[0073] 1. Add 2 μL of the compound into 85 μL of double-distilled water (add 2 μL of double-distilled water to the control group).

[0074] 2. Add 10 μL of 10× buffer and 2 μL of HeLa nuclear aspirated body fluid to each well.

[0075] 3. Add 5 μL of HDAC fluorescent substrate and incubate in a 37°C inc...

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PUM

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Abstract

The invention discloses a novel hydroxamic acid micromolecule organic compound with a thaizolidinone structure represented by a formula (1) or (II), hydroximic acid derivatives, pharmaceutically acceptable salts and a preparation method of the hydroxamic acid micromolecule organic compound as well as application of the hydroxamic acid micromolecule organic compound in the preparation of medicaments for treating diseases such as tumor growth, transfer and relapse. The invention further discloses a pharmaceutical composition containing the hydroxamic acid micromolecule organic compound.

Description

technical field [0001] The present invention belongs to the field of medicine, and specifically relates to hydroxamic acid small molecular organic compounds containing thiazolinone structures represented by formula (I) and formula (II) and hydroxamic acid derivatives or pharmaceutically acceptable salts thereof. Its preparation method, and its pharmaceutical application. Background technique [0002] Traditionally, tumors are considered to be genetic defect diseases caused by gene mutations, deletions, and chromosomal abnormalities. Gene mutations, deletions, and chromosomal abnormalities usually result in loss of activity of some tumor suppressor genes and high activation of proto-oncogenes. However, accumulating evidence indicates that epigenetic regulation of gene expression is critical in tumorigenesis and progression. [0003] Chromatin remodeling between "on" and "off" plays an important role in epigenetically regulated gene expression. This remodeling is the result...

Claims

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Application Information

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IPC IPC(8): C07D277/14C07D417/04C07D417/14A61K31/426A61K31/427A61K31/506A61P35/00A61P35/02
CPCC07D277/14C07D417/04C07D417/14
Inventor 陈益华刘明耀李静婕杨飞飞易正芳彭世鸿
Owner EAST CHINA NORMAL UNIV
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