Benzofuran derivative, preparation method and application thereof

A technology for benzofuran and derivatives, which is applied in the fields of preparing antiarrhythmic drugs and treating related diseases, and can solve the problems of poor water solubility, oral bioavailability of liver first-pass effect and the like

Active Publication Date: 2016-02-10
CHINA RESOURCES SAIKE PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] In order to overcome the disadvantages of poor water solubility of dronedarone hydrochloride, easy hepatic first-pass effect in vivo and low oral bioavailability, the presen

Method used

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  • Benzofuran derivative, preparation method and application thereof
  • Benzofuran derivative, preparation method and application thereof
  • Benzofuran derivative, preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

preparation Embodiment 1

[0077] Preparation Example 12-Butyl-3-[4-(3-chloropropoxy)benzoyl]-5-nitrobenzofuran

[0078] 2-Butyl-3-(4-hydroxybenzoyl)-5-nitrobenzofuran (33.94g, 100mmol) was added to 300ml of 95% acetonitrile aqueous solution, potassium carbonate (27.64g, 200mmol) and tetrabutyl Ammonium bromide (1.61g, 5mmol), heated to reflux for 20min, added 1-bromo-3-chloropropane (17.32g, 110mmol), refluxed for 17h, cooled the reaction solution to room temperature, filtered, and washed the filter cake with a small amount of acetonitrile, The filtrate was concentrated, and the residue was separated and purified by silica gel column (eluent, petroleum ether:ethyl acetate=10:1, v:v) to obtain 28.3 g of light yellow solid with a yield of 68%.

preparation Embodiment 2

[0079] Preparation Example 22-Butyl-3-[4-[3-(piperidin-1-yl)propoxy]benzoyl]-5-nitrobenzofuran

[0080] 2-Butyl-3-[4-(3-chloropropoxy)benzoyl]-5-nitrobenzofuran (8.32g, 20mmol) was dissolved in 60ml of acetonitrile, piperidine (2.56g, 30mmol), potassium carbonate (8.29g, 60mmol) and potassium iodide (0.33g, 2mmol), reflux reaction for 24h, the reaction solution was cooled to room temperature, filtered, the filter cake was washed with a small amount of acetonitrile, and the filtrate was concentrated. The residue was dissolved in 60m ethyl acetate, washed with saturated brine (50ml×2) and water (50ml×2), the organic layer was dried over anhydrous sodium sulfate, filtered and concentrated to give 8.08g yellow oil, the yield was 87%.

preparation Embodiment 3

[0081] Preparation Example 32-Butyl-3-[4-[3-(piperidin-1-yl)propoxy]benzoyl]-5-aminobenzofuran

[0082] 2-Butyl-3-[4-[3-(piperidin-1-yl)propoxy]benzoyl]-5-nitrobenzofuran (4.65g, 10mmol) was dissolved in 45ml of absolute ethanol 0.93g of palladium carbon was added, the reaction system was filled with hydrogen three times, and reacted at 50°C for 16h under the condition of flowing hydrogen. The reaction solution was cooled to room temperature, filtered, the filter cake was washed with a small amount of absolute ethanol, and the filtrate was concentrated to obtain 4.15 g of a yellow oil with a yield of 95%.

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Abstract

The invention discloses a benzofuran derivative represented as the formula (I) or a pharmaceutically acceptable salt thereof, a preparation method thereof and an application thereof in preparation of an anti-arrhythmic drug, wherein the groups are defined as in the specification.

Description

technical field [0001] The invention belongs to the field of medicine, in particular, the invention relates to a benzofuran derivative or a pharmaceutically acceptable salt thereof, a preparation method of the derivative, a pharmaceutical composition containing the derivative, and the derivative and Use of the pharmaceutical composition in preparing antiarrhythmic drugs and treating related diseases. Background technique [0002] Amiodarone belongs to benzofuran derivatives and is used for the prevention and treatment of ventricular arrhythmia and atrial fibrillation. It has been used clinically as an antiarrhythmic drug for more than 40 years. Since the molecular structure of amiodarone contains 2 iodine atoms, accounting for 37.2% of its relative molecular weight, after 2 to 3 months of treatment, thyroid dysfunction occurs in about 5% to 28% of patients. Long-term administration of amiodarone has an increased risk of adverse reactions, among which pulmonary toxicity is t...

Claims

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Application Information

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IPC IPC(8): C07D307/80C07D405/12A61K31/5377A61K31/4525A61K31/4025A61K31/343A61P9/06
CPCC07D307/80A61K31/343A61K31/4025A61K31/4525A61K31/5377C07D405/12
Inventor 王文峰杨琰李日东郑满冬
Owner CHINA RESOURCES SAIKE PHARMA
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