Coumarin azole compound with antimicrobial activity, and preparation method and medicinal application thereof

A technology of coumarin azoles and compounds, applied in the direction of organic active ingredients, medical preparations containing active ingredients, organic chemistry, etc., can solve the problems of drug resistance, toxic and side effects, etc., and achieve low cost, simple synthesis method, and raw materials Easy to get effect

Inactive Publication Date: 2011-05-04
SOUTHWEST UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Commonly used anti-infective drugs of this type include novobiocin, clonobiocin, coumomycin, etc., while they have played a huge role in effectively c

Method used

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  • Coumarin azole compound with antimicrobial activity, and preparation method and medicinal application thereof
  • Coumarin azole compound with antimicrobial activity, and preparation method and medicinal application thereof
  • Coumarin azole compound with antimicrobial activity, and preparation method and medicinal application thereof

Examples

Experimental program
Comparison scheme
Effect test

Example Embodiment

[0031] Example 1: Preparation of 7-(2-(1H-1,2,4-triazol-1-yl)-ethoxy)-4-methyl-coumarin (abbreviated as compound 1)

[0032] In a 100 mL single-neck round bottom flask, add 30 mL of acetonitrile, 4.141 g (30.0 mmol) of anhydrous potassium carbonate, 1.321 g (20.0 mmol) of 1,2,4-triazole, and stir at room temperature for 1 hour. Add 7-(2- Bromo-ethoxy)-4-methylcoumarin 2.820g (10.0mmol), TLC tracked until the reaction was completed, acetonitrile was distilled off under reduced pressure, the remaining solid was added with 100mL of water, extracted three times with an equal volume of chloroform, and the organic layers were combined. The organic layer was back-extracted with saturated brine once, and the organic layer was dried with anhydrous sodium sulfate. Concentrate the organic phase and perform column chromatography (using chloroform and acetone (3 / 1, V / V) as eluents) to obtain 2.093 g of white solid, yield: 77.2%; melting point: 199~201°C; 1 H NMR(400MHz, CDCl 3 )δ: 8.11(s, 1H,...

Example Embodiment

[0033] Example 2: Preparation of 7-(3-(1H-1,2,4-triazol-1-yl)-propoxy)-4-methyl-coumarin (abbreviated as compound 2)

[0034] According to the synthesis method in Example 1. Starting materials 30mL acetonitrile, 4.140g (30.0mmol) of anhydrous potassium carbonate, 1.321g (20.0mmol) of 1,2,4-triazole, 7-(3-bromo-propoxy)-4-methyl coumarone 2.960 g (10.0 mmol) of sodium sulfate to obtain 2.221 g of white solid, yield: 77.9%; melting point: 145-146°C; 1 HNMR(400MHz, CDCl 3 )δ: 8.09(s, 1H, triazole 3-H), 7.97(s, 1H, triazole 5-H), 7.50~7.48(d, 1H, coumarin 5-H), 6.83~6.78(m, 2H, coumarin 6,8-H), 6.14(s, 1H, coumarin 3-H), 4.44~4.42(m, 2H, coumarin-OCH 2 ), 4.00~3.99(m, 2H, triazole-CH 2 ), 2.43~2.40(m, 5H, Ar-CH 3 , Triazole-CH 2 CH 2 )ppm.

Example Embodiment

[0035] Example 3: Preparation of 7-(4-(1H-1,2,4-triazol-1-yl)-butoxy)-4-methyl-coumarin (abbreviated as compound 3)

[0036] According to the synthesis method in Example 1. The starting materials are 30mL of acetonitrile, 4.141g (30.0mmol) of anhydrous potassium carbonate, 1.321g (20.0mmol) of 1,2,4-triazole, 7-(4-bromo-butoxy)-4-methyl incense 3.101g (10.0mmol) of legume, to obtain 2.300g of white solid, yield: 76.9%; melting point: 85-86°C; 1 H NMR(400MHz, CDCl 3 )δ: 8.13(s, 1H, triazole 3-H), 7.96(s, 1H, triazole 5-H), 7.50~7.48(d, 1H, coumarin 5-H), 6.84~6.78(m, 2H, coumarin 6,8-H), 6.13(s, 1H, coumarin 3-H), 4.28~4.26(m, 2H, coumarin-OCH 2 ), 4.04~4.03(m, 2H, triazole-CH 2 ), 2.39(s, 1H, Ar-CH 3 ), 2.14~2.11(m, 4H, coumarin-OCH 2 CH 2 , Triazole-CH 2 CH 2 )ppm.

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Abstract

The invention relates to a coumarin azole compound with antimicrobial activity and pharmaceutically acceptable salt thereof, wherein the coumarin azole compound has a structural general formula shown in the specifications. The invention also relates to a preparation method of the coumarin azole compound and the pharmaceutically acceptable salt of the coumarin azole compound. The method comprises the following steps of: synthesizing an intermediate compound, namely 7-hydroxy coumarin by using substituted phenols and acyl acetic acid ester as raw materials; reacting the 7-hydroxy coumarin with dihalide to obtain a haloalkyl/aralkyl/aryl-cumarin intermediate; reacting the haloalkyl/aralkyl/aryl-cumarin intermediate with a series of azole compounds to obtain the coumarin azole compound; and converting the coumarin azole compound into nitrate, hydrochloride or acetate. The invention also relates to the medicinal application of the coumarin azole compound, the pharmaceutically acceptable salt of the coumarin azole compound, and a medicinal composition of the coumarin azole compound and the pharmaceutically acceptable salt of the coumarin azole compound.

Description

technical field [0001] The invention relates to the fields of organic chemistry and pharmacy, in particular to the design of coumarin azole compounds, and also relates to the preparation and biological activity of coumarin azole compounds and pharmaceutically acceptable salts thereof. The invention also relates to the medical use of such compounds. Background technique [0002] Antibacterial drugs are a class of drugs for the treatment of bacterial infections. There are many types, such as β-lactams, macrolides, aminoglycosides, tetracyclines, quinolones, sulfonamides, oxazolidinones, etc. However, due to the change of outer membrane permeability to block drug entry, the production of certain enzymes to inactivate antibiotics, the variation of the target site leads to non-response to drugs, the increase of efflux and accelerated pumping of drugs into the bacteria, etc. Bacterial resistance is increasing. Whether it is Gram-positive bacteria or Gram-negative bacteria, a var...

Claims

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Application Information

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IPC IPC(8): C07D405/12A61K31/4196A61K31/4192A61K31/4178A61K31/4184A61P31/04A61P31/10A61P31/18
Inventor 周成合时园万昆
Owner SOUTHWEST UNIVERSITY
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