Series of diphenyl oxide derivatives and use of diphenyl oxide derivatives in preparation of anti-tuberculosis drugs

A technology of biphenyl ether and tuberculosis, applied in the field of chemical medicine, can solve the problems of long treatment cycle, poor effect and complexity of immunosuppressed patients, and achieve good effect of inhibiting activity in vitro

Inactive Publication Date: 2014-04-09
SICHUAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the current standard tuberculosis therapy cycle is long and complicated, and it is not effective for immunosuppressed patients. Therefore, it is urgent to discover potential new anti-tuberculosis drug targets, develop drugs that can effectively treat drug-resistant tuberculosis and latent tuberculosis infection, and shorten treatment. cycle of drugs

Method used

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  • Series of diphenyl oxide derivatives and use of diphenyl oxide derivatives in preparation of anti-tuberculosis drugs
  • Series of diphenyl oxide derivatives and use of diphenyl oxide derivatives in preparation of anti-tuberculosis drugs
  • Series of diphenyl oxide derivatives and use of diphenyl oxide derivatives in preparation of anti-tuberculosis drugs

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0017] Example 1 : the preparation of ethyl 3-phenoxyphenylacetate (3a)

[0018]

[0019] Weigh 10.80g of ethyl m-hydroxyphenylacetate (1a), dissolve it in 100mL of dioxane, add 5.60mL of iodobenzene (2a), 4.76g of cuprous iodide, 7.73g of N,N-dimethylglycine, carbonic acid Cesium 32.58g, heated up to 100°C under the protection of nitrogen, stopped the reaction after 24 hours of reaction, removed the solvent by rotary evaporation, added water and ethyl acetate to separate the layers, extracted the water layer with ethyl acetate three times, combined the organic layers, washed once with saturated brine, Add anhydrous sodium sulfate to dry, concentrate and purify by column chromatography to obtain 10.15 g of light yellow oily substance (3a) with a yield of 79.2%. 1 H-NMR (400MHz, CDCl 3 - d 6 ) δ : 7.31-7.35 (m, 2H), 7.27 (t, J = 8.0 Hz, 1H), 7.10 (t, J = 7.6 Hz, 1H), 7.00-7.02 (m, 3H), 6.95 (s, 1H), 6.90 (dd, J = 8.0, 2.0 Hz, 1H), 4.14 (qua, J = 7.2 Hz, 2H), 3...

Embodiment 2

[0020] Example 2 : the preparation of 3-phenoxyphenylacetic acid (4a)

[0021]

[0022] Weigh 6.41 g of ethyl 3-phenoxyphenylacetate (3a), add 5 g of KOH and 100 mL of water, heat to reflux for 5 hours, stop the reaction, adjust the pH to 2 with concentrated hydrochloric acid, at this time a large amount of light yellow solid powder is precipitated, Filter and wash with water until neutral, and dry in vacuo to obtain 5.43 g of light yellow solid 3-phenoxyphenylacetic acid (4a), with a yield of 95.3%. 1 H-NMR (400MHz, CDCl 3 - d 6 ) δ : 7.75-9.82 (br, 1H), 7.33-7.37 (m, 2H), 7.29 (t, J = 8.0 Hz, 1H), 7.12 (t, J = 7.6 Hz, 1H), 7.01-7.03 (m, 3H), 6.96 (s, 1H), 6.92 (dd, J = 8.0, 2.0 Hz, 1H), 3.63(s, 2H).

Embodiment 3

[0023] Example 3: Preparation of N-(3,4-dichlorophenyl)-2-(3-phenoxyphenyl)acetamide (6a)

[0024]

[0025] Weigh 2.28g of 3-phenoxyphenylacetic acid (4a), add 20mL of anhydrous chloroform, 15mL of thionyl chloride, heat to reflux for 2 hours, evaporate the solvent under reduced pressure, add anhydrous toluene 5mL after mixing, Continue to pressurize and evaporate to dryness to obtain a yellow oil. Dissolve the obtained yellow oil in 5 mL of anhydrous dichloromethane, add 1.74 mL of triethylamine and 1.77 g of 3,4-dichloroaniline in 10 mL of dichloromethane solution under ice cooling, stir at room temperature for 8 h, stop the reaction, and use 20 mL×3 washed three times with water, washed once with saturated brine, dried by adding anhydrous sodium sulfate, filtered, and spin-dried to obtain a yellow solid, purified by column chromatography to obtain a white solid N-(3,4-dichlorophenyl)-2 -(3-phenoxyphenyl)acetamide (6a) 1.86g, yield 50.13%. Melting point: 132.9-133.6 ...

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PUM

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Abstract

The present invention relates to a series of diphenyl oxide derivatives and a use of the diphenyl oxide derivatives in preparation of anti-tuberculosis drugs, and belongs to the field of chemical medicine. Specifically the present invention relates to a use of a compound represented by a formula (I), wherein Ar1 is a substituted benzene ring, n is an integer of 0-3, R1 is a substituted benzene ring Ar2 or a substituted heterocyclic Het. The test results show that the compound represented by the formula (I) provides good in vitro inhibition activity for tubercle bacillus H37Rv, provides a good treatment effect for in vivo BCG infection mice model, and provides a new selection for preparation of the anti-tuberculosis drugs.

Description

technical field [0001] The invention belongs to the field of chemical medicine, in particular to a class of biphenyl ether derivatives and their application in the preparation of anti-tuberculosis drugs. Background technique [0002] Tuberculosis (TB) is caused by Mycobacterium tuberculosis ( Mycobacterium tuberculosis , MTB) is the second deadliest infectious disease after AIDS. According to the report of the World Health Organization, about 1 / 3 of the people in the world are infected with tuberculosis, with 8 million new cases and 2 million deaths every year. The 2010 Global TB Control Report shows that in 2009 there were 9.4 million cases worldwide, of which 170 died from TB. With the increasing number of HIV-positive TB patients and the emergence of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB), the treatment of TB is becoming more and more challenging. However, the current standard tuberculosis therapy cycle is long an...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07C235/38C07C255/60C07D277/82C07D213/75C07D277/46A61K31/167A61K31/165A61K31/428A61K31/277A61K31/44A61K31/426A61P31/06
Inventor 罗有福王震铃魏于全
Owner SICHUAN UNIV
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