Diaryl urea compounds containing quinazolinone and preparation method and application thereof

A technology of diaryl urea and quinazolinone, which is applied in the field of biomedicine, can solve the problems of affecting the treatment of patients, aggravating the pain and burden of patients, and achieve the effect of reducing anaphylaxis, alleviating pain and burden, and cheap reagents

Active Publication Date: 2020-05-22
XI AN JIAOTONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Drug anaphylaxis not only limits the normal use of many drugs, affects the treatment of patients, but also increases the pain and burden of patients

Method used

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  • Diaryl urea compounds containing quinazolinone and preparation method and application thereof
  • Diaryl urea compounds containing quinazolinone and preparation method and application thereof
  • Diaryl urea compounds containing quinazolinone and preparation method and application thereof

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preparation example Construction

[0040] The preparation method 1 of the diarylurea compound containing quinazolinone includes the following steps:

[0041] 1) 2-Amino-4-fluorobenzoic acid and formamide are cyclized to prepare 7-fluoroquinazolin-4(3H)-one;

[0042] 2) Preparation of 7-((4-aminophenyl)thio)quinazolin-4(3H)-one by nucleophilic substitution reaction between 7-fluoroquinazolin-4(3H)-one and p-aminothiophenol;

[0043] 3) Diarylurea compounds containing quinazolinones are obtained by nucleophilic reaction between phenyl isocyanate containing substituents and 7-((4-aminophenyl)thio)quinazolin-4(3H)-one.

[0044] Preferably, in step 1) of preparation method 1, 2-amino-4-fluorobenzoic acid is dissolved in formamide and reacted at 160°C under nitrogen protection. After the reaction is completed, the reaction solution is poured into ice water and filtered, The filter cake was recrystallized from methanol to obtain 7-fluoroquinazolin-4(3H)-one.

[0045] Preferably, in step 2) of Preparation Method 1, 7-fluoroquin...

Embodiment 1

[0057] 1) 2-Amino-4-fluorobenzoic acid (compound 1) and formamide are cyclized to prepare 7-fluoroquinazolin-4(3H)-one (compound 2);

[0058] Weigh 10.0 g of compound 1 and dissolve it in 30 mL of formamide, and react at 160° C. for 6 h under nitrogen protection. After the reaction is completed, the reaction solution is poured into ice water, filtered, and the filter cake is recrystallized with methanol to obtain compound 2.

[0059] 2) Preparation of 7-((4-aminophenyl)thio)quinazoline-4 by substitution reaction of 7-bromoquinazoline-4(3H)-one (compound 2) and p-aminothiophenol (compound 3) (3H)-ketone (compound 4);

[0060] Compound 2 2.0g, K 2 CO 3 1.26g was added to 10mL dimethyl sulfoxide, protected by argon, and the temperature was raised to 115℃; p-aminothiophenol 3 1.14g dimethyl sulfoxide (5mL) solution was added dropwise to the above reaction solution and reacted for 1h After the reaction, the reaction solution was poured into ice water, extracted with ethyl acetate, the o...

Embodiment 2

[0064] 1) 2-Amino-4-bromobenzoic acid (compound 7) and formamide are cyclized to prepare 7-bromoquinazolin-4(3H)-one (compound 8);

[0065] Use an analytical balance to weigh 5.1 g of compound 7 into a 250 mL round bottom flask, and add 100 mL of formamide solution, N 2 Microwave reaction under protection (150°C, 1.45h); after the reaction is over, ice water is added while hot, extracted with ethyl acetate, the organic phase is concentrated and left standing to precipitate a solid, which is suction filtered. The resulting filter cake is compound 8.

[0066] 2) 7-((4-nitrophenyl)thio)quinazoline-4 is prepared by reaction of 7-bromoquinazoline-4(3H)-one (compound 8) and p-nitrothiophenol (compound 9) (3H)-ketone (compound 10);

[0067] Compound 8 0.5g, p-nitrothiophenol 1.02g, K 2 CO 3 0.3g and 0.02g CuI were added to a 100mL round bottom flask. Under ice bath conditions, vacuum and nitrogen protection were applied. Then the temperature was raised to 130°C and reacted for 6h; after t...

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Abstract

The invention provides a quinazolinone-containing diaryl urea compound and a preparation method and application thereof. The quinazolinone-containing diaryl urea compound can obviously inhibit LAD2 cells from releasing beta-hexosaminidase, shows obvious dosage association, can be used for preparing an antiallergic medicament, and particularly can be used for preparing a medicament for antagonizingLAD2 cells from releasing beta-hexosaminidase so as to reduce pain and a load of a patient. The preparation method provided by the invention is easy in obtaining of raw material sources, mild in reaction condition, simple in operation in the reaction process and cheap in used reagent.

Description

Technical field [0001] The invention belongs to the technical field of biomedicine, and relates to a diarylurea compound containing quinazolinone and a preparation method and application thereof. Background technique [0002] Drug-like allergic reactions refer to: Many drugs used in clinical practice are neither antigens nor haptens. They react when they first come into contact with the body. The clinical manifestations are similar to allergic reactions, which are called allergic reactions. Allergic reactions account for a large proportion of drug allergy cases. Drug-like allergic reactions not only limit the normal use of many drugs, but also affect the treatment of patients, and increase the pain and burden of patients. The detection of β-hexosaminidase release is widely used in the clinical and laboratory characterization and evaluation of allergic reactions. Therefore, the preparation of compounds that antagonize the release of β-hexosaminidase from LAD2 cells for the devel...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D239/88A61K31/517A61P37/08
CPCC07D239/88
Inventor 贺浪冲张涛贺怀贞张杰卢闻潘晓艳史先鹏车德路
Owner XI AN JIAOTONG UNIV
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