Isoquinolone derivative as well as preparation method and application thereof

A technology of isoquinolinone and its derivatives, which is applied in the field of preparation of isoquinolinone derivatives and their pharmacologically acceptable salts, esters, prodrugs, and can solve the problem of harsh reaction conditions, high cost and low yield And other issues

Inactive Publication Date: 2017-10-24
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The above-mentioned synthetic method has limited its application in pharmaceutical production due to the harsh reaction conditions, low yield, high cost, and heavy metal residues.

Method used

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  • Isoquinolone derivative as well as preparation method and application thereof
  • Isoquinolone derivative as well as preparation method and application thereof
  • Isoquinolone derivative as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036] Example 1 Synthesis of some compounds of the present invention, including Ia-Il and IIa-IIc, taking compound Ia as an example.

[0037] N, the preparation of N-dibenzyl-2-hydroxybenzamide:

[0038]

[0039] Dissolve 1 g (7.25 mmol) of salicylic acid in 30 mL of anhydrous dichloromethane, add 1.05 mL (14.5 mmol) of thionyl chloride, 1 drop of N,N-dimethylformamide, and heat up to reflux for 2 hours. Cool to room temperature, spin dry the solvent, dissolve in anhydrous dichloromethane, and add dropwise to anhydrous dichloromethane solution containing 3.10mL (21.75mmol) of triethylamine and 1.48g (7.25mmol) of dibenzylamine. After the dropwise addition was completed, the mixture was stirred at room temperature for 5 min, and spin-dried to obtain a crude product, which was purified by column chromatography to obtain 1.95 g of white solid N,N-dibenzyl-2-hydroxybenzamide, with a yield of 85%. 1 H NMR (300MHz, CDCl 3 )δ4.72(s, 4H), 6.77(td, J=7.6, 1.2Hz, 1H), 6.99-7.10(m,...

Embodiment 2

[0085] Example 2 Antitumor Activity Experiment of Compounds Ia-Il, IIa-IIc.

[0086] Experimental Materials:

[0087] Cell line: human cervical cancer cell HeLa and human breast cancer cell MCF-7; sample: compound Ia-Il, IIa-IIc added appropriate amount of DMSO to make the concentration of 10 -2 M solution, diluted with culture medium to the corresponding concentration before use.

[0088] experimental method:

[0089] Cell digestion and counting, 2.5×10 per well 3 Spot cells in a 96-well plate, with a total volume of 100 μL per well, culture for 24 hours, dilute the sample to be tested to an appropriate concentration with medium, 100 μL per well, set up 3 duplicate wells, add 20 μL of 5 mg / mL MTT solution after 72 hours of culture After incubation for 4 hours, suck out all the liquid in the well, add 100 μL DMSO, and measure the absorbance with a full-wavelength microplate reader. Calculate the inhibition rate according to the absorbance value, and the calculation formula...

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PUM

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Abstract

The invention relates to an isoquinolone derivative as well as a preparation method and application thereof. According to a synthesis method, the isoquinolone derivative is prepared from various substituted acetamides as the raw material and a nonmetal as a catalyst under the action of an initiator. Compared with an existing synthesis method, the synthesis method provided by the invention is more economical and environment-friendly, and use of a metal catalyst is avoided. In addition, the synthesis method also has the advantages of being simple in operation, wide in atom economy and wide in substrate adaptability. Furthermore, the compound has a good application prospect in the aspects, such as tumors, cardiovascular diseases, inflammatory diseases, metabolic diseases and neurodegenerative diseases.

Description

technical field [0001] The invention belongs to the field of medicinal chemistry, and specifically relates to formula (I), isoquinolinone derivatives shown in formula (II) and their pharmacologically acceptable salts, esters and prodrugs and their preparation methods and their therapeutic effects on tumors and heart disease. Applications in vascular diseases, inflammatory diseases, metabolic diseases, neurodegenerative diseases, etc. [0002] Background technique [0003] Tumor is the most common and one of the most threatening diseases to human health, seriously affecting human production and life. According to domestic statistics, lung cancer is the tumor with the highest incidence rate, followed by gastric cancer, esophageal cancer and liver cancer. At present, there are many anti-tumor drugs on the market, but these anti-tumor drugs show defects such as poor selectivity, high toxicity and side effects, and easy drug resistance in clinical use. Therefore, it is partic...

Claims

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Application Information

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IPC IPC(8): C07D265/22C07D498/04C07D239/91C07D471/04A61P35/00A61P9/00A61P29/00A61P3/00A61P25/28
CPCC07D239/91C07D265/22C07D471/04C07D498/04
Inventor 王进欣高彪陈凯丽尤启冬毕小玲郭琦
Owner CHINA PHARM UNIV
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