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Quinazolinone-containing diaryl urea compound 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 anaphylactoid reactions, reducing pain and burden, and cheap reagents

Active Publication Date: 2018-03-20
XI AN JIAOTONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

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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  • Quinazolinone-containing diaryl urea compound and preparation method and application thereof
  • Quinazolinone-containing diaryl urea compound and preparation method and application thereof
  • Quinazolinone-containing diaryl urea compound and preparation method and application thereof

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preparation example Construction

[0040] The preparation method 1 of the described diaryl urea compound containing quinazolinone comprises the following steps:

[0041] 1) 2-amino-4-fluorobenzoic acid and formamide prepare 7-fluoroquinazolin-4(3H)-one by ring closure reaction;

[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) Nucleophilic reaction of phenyl isocyanate with substituent and 7-((4-aminophenyl)thio)quinazolin-4(3H)-one to obtain diaryl urea compound containing quinazolinone.

[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 give 7-fluoroquinazolin-4(3H)-one.

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

Embodiment 1

[0057] 1) Preparation of 7-fluoroquinazolin-4(3H)-one (compound 2) by cyclization reaction of 2-amino-4-fluorobenzoic acid (compound 1) and formamide;

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

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

[0060] Compound 2 2.0 g, K 2 CO 3 1.26g was added to 10mL dimethyl sulfoxide, under argon protection, the temperature was raised to 115°C; a solution of 1.14g of p-aminothiophenol 3 in dimethyl sulfoxide (5mL) was added dropwise to the above reaction solution, and reacted for 1h After the reaction, the reaction solution was poured into ice water, e...

Embodiment 2

[0064] 1) Preparation of 7-bromoquinazolin-4(3H)-one (compound 8) by cyclization reaction of 2-amino-4-bromobenzoic acid (compound 7) and formamide;

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

[0066] 2) Preparation of 7-((4-nitrophenyl)thio)quinazoline-4 by reacting 7-bromoquinazolin-4(3H)-one (compound 8) with p-nitrothiophenol (compound 9) (3H)-ketone (compound 10);

[0067] Compound 8 0.5g, p-nitrothiophenol 1.02g, K 2 CO 3 Add 0.3g and 0.02g of CuI into a 100mL round-bottomed flask. Under the condition of ice bath, vacuum nitrogen protection, then raise the temperature to 130°C, and react for 6h;

[0068] 3) 7-((4...

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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 diaryl urea compound containing quinazolinone, a preparation method and application thereof. Background technique [0002] The anaphylactoid reaction of drugs refers to: many drugs used clinically are neither antigens nor haptens, and react when they come into contact with the body for the first time, and the clinical manifestations are similar to allergic reactions, which are called anaphylactoid reactions. Anaphylactoid reactions account for a large proportion of drug allergy cases. 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. The detection of β-hexosaminidase release is widely used in the characterization and evaluation of anaphylactoid reactions at clinical and laboratory levels. Therefore, the preparation of compounds that antagonize the release of β-hexosaminidase ...

Claims

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Application Information

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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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