Application of 3-aryl benzofuran derivative EAPP-2 in preparation of medicine for treating chronic obstructive pulmonary disease

A technology of EAPP-2 and chronic obstructive pulmonary disease, which is applied in the preparation of 3-arylbenzofuran derivative EAPP-2 or a pharmaceutically acceptable salt thereof, in the preparation of drugs for the prevention and/or treatment of chronic obstructive pulmonary disease Application field, achieve significant anti-inflammatory activity in vivo and in vitro, easy to standardize production, and significant inhibitory effect

Pending Publication Date: 2022-03-01
INST OF MATERIA MEDICA CHINESE ACAD OF MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Pharmacological studies have shown that the compound has a significant therapeutic effect on chronic obstructive pulmonary disease, and the application of the compound in the treatment and / or prevention of chronic obstructive pulmonary disease has not been reported yet

Method used

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  • Application of 3-aryl benzofuran derivative EAPP-2 in preparation of medicine for treating chronic obstructive pulmonary disease
  • Application of 3-aryl benzofuran derivative EAPP-2 in preparation of medicine for treating chronic obstructive pulmonary disease
  • Application of 3-aryl benzofuran derivative EAPP-2 in preparation of medicine for treating chronic obstructive pulmonary disease

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0049] Example 1: Preparation of compound (I) [3-(3,5-dimethoxyphenyl)-6-methoxy-4-benzofurancarboxylic acid-4-acetylphenyl ester].

[0050] The synthetic steps of compound EAPP-2 (I) are as follows:

[0051] Step 1: Synthesis of α-phenoxyketocarboxylic acid through etherification reaction between methyl 3-methoxy-5-hydroxybenzoate and 1-(3,5-dimethoxyphenyl)-2-bromoacetophenone methyl ester.

[0052] Methyl 3-methoxy-5-hydroxybenzoate (4.5g, 26.8mmol) was dissolved in 1-(3,5-dimethoxyphenyl)-2-bromoacetophenone (6.94g, 26.8mmol) In 150ml of dry acetone, slowly add K under vigorous stirring 2 CO 3 The solid was 7.39g (53.5mmol), and the reaction solution was stirred at room temperature for 3h, and then heated to reflux for 3h. TLC monitoring showed that the reaction of raw materials was complete. The reaction solution was cooled to room temperature, filtered with diatomaceous earth, washed with acetone, and the organic phase was concentrated under reduced pressure. The ob...

experiment example 1

[0064] Experimental example 1: Effect of EAPP-2 on LPS-induced HL-60 neutrophil inflammation in vitro

[0065] experimental method:

[0066] HL-60 is a neutrophil promyelocyte that can be induced to differentiate into a monocyte, macrophage or neutrophil phenotype. Using DMSO as an inducer to induce HL-60 to differentiate into neutrophil-like cells, under the induction of bacterial lipopolysaccharide LPS can produce inflammatory factors such as chemotactic factor IL-8, participate in and mediate the inflammatory response. By detecting the amount of IL-8 produced in the medium supernatant of HL-60 differentiated neutrophil-like cells induced by LPS, the anti-inflammatory activity of the compound can be preliminarily observed in vitro.

[0067] experimental method:

[0068] HL-60 cells in good growth state and in logarithmic growth phase were taken and cultured with RPMI-1640 medium containing 10% FBS and 1.25% DMSO for 5-6 days to induce HL-60 to differentiate into neutrophil...

experiment example 2

[0074] Experimental Example 2: Effect of EAPP-2 on LPS-induced secretion of inflammatory cytokines from mouse bone marrow-derived neutrophils

[0075] Experimental method: Take several SPF grade male BALB / c mice, kill them, and aseptically peel off the femur and tibia, cut off the two ends of the femur and tibia, and expose the red bone marrow cavity, take a 1ml sterile syringe, and draw 5% serum 1640 medium, flush the bone marrow cavity to obtain bone marrow. The final preparation is 2×10 8 ~1×10 9 / ml of bone marrow single cell suspension for use; use the mouse bone marrow neutrophil separation kit to separate neutrophils. Mouse bone marrow neutrophils were inoculated in a 96-well plate, and compounds of different concentrations were added for pre-protection for 1 h. After 1 h, LPS (final concentration was 1 μg / mL) was added to the well plate, and the cells were incubated at 37°C, 5% CO 2 Incubate in the environment for 6 hours; after 6 hours, absorb the supernatant of th...

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Abstract

The invention belongs to the field of biological medicines, and discloses application of a 3-aryl benzofuran derivative EAPP-2 shown as a formula (I) in preparation of a medicine for treating and / or preventing chronic obstructive pulmonary diseases. The 3-aryl benzofuran derivative EAPP-2 disclosed by the invention is simple in preparation method, has obvious anti-inflammatory activity, has an obvious treatment effect on chronic obstructive pulmonary diseases, has an improvement effect on pathological changes of lung tissue inflammation of a COPD (chronic obstructive pulmonary disease) model mouse, and can be used for preparing medicines for treating chronic obstructive pulmonary diseases. Various indexes of COPD airway inflammation can be improved, collection of the total number of leukocytes, neutrophil and macrophages in BALF is remarkably inhibited, the generation level of inflammatory factors TNF-alpha, IL-17A, IFN-gamma and the like in BALF is remarkably reduced, the compound can be applied to clinical treatment of chronic obstructive pulmonary diseases in the form of a monomer or a medicinal composition, and the compound can be applied to clinical treatment of chronic obstructive pulmonary diseases. The potential application value is realized on the treatment of chronic obstructive pulmonary diseases and immune-related diseases.

Description

technical field [0001] The present invention relates to the field of biomedicine, in particular to a 3-arylbenzofuran derivative EAPP-2 or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition containing the derivative or a pharmaceutically acceptable salt thereof , application in the preparation of medicaments for preventing and / or treating chronic obstructive pulmonary disease. Background technique [0002] Chronic obstructive pulmonary disease (COPD) is a progressive respiratory disease characterized by incompletely reversible airflow limitation, which is characterized by high morbidity, disability and mortality. The incidence rate over the age of 9 has been as high as 9%-10%, and it is still increasing year by year, seriously endangering global human health. [0003] Airflow limitation in COPD is associated with an abnormal chronic inflammatory response of the airways and lungs to noxious particles or gases. Chronic airway inflammation is an impo...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/343A61K45/06A61P11/00A61P29/00
CPCA61K31/343A61K45/06A61P11/00A61P29/00
Inventor 林明宝姚春所侯琦马培张梓倩范燕楠范旖瑶苏福宝袁继巧
Owner INST OF MATERIA MEDICA CHINESE ACAD OF MEDICAL SCI
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