Paeonol dihydropyrimidinone derivatives and preparation method and application thereof

A technology of paeonol dihydropyrimidinone and derivatives is applied in the field of paeonol dihydropyrimidinone derivatives and preparation thereof, and can solve the problems that no public reports of dihydropyrimidinone derivatives have been reported, and achieves The effect of high purity, improved antitumor activity, and short preparation cycle

Active Publication Date: 2022-07-19
GUILIN MEDICAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] Although many structural modifications of paeonol have been reported in the existing literature to obtain a series of paeonol derivatives, there is no such thing as combining paeonol with dihydropyrimidinone to obtain paeonol dihydropyrimidinone derivatives. public reporting

Method used

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  • Paeonol dihydropyrimidinone derivatives and preparation method and application thereof
  • Paeonol dihydropyrimidinone derivatives and preparation method and application thereof
  • Paeonol dihydropyrimidinone derivatives and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0045] Example 1: Preparation of 2-(4-bromobutoxy)-4-methoxyacetophenone (Compound 2)

[0046] 15.0 mmol of paeonol 1 and 15.0 mmol of anhydrous potassium carbonate were added to a 250 ml round-bottomed flask, dissolved in 150 mmol of acetone, and 48.0 mmol of 1,4-dibromobutane was added under stirring at room temperature, and the reaction was stirred at room temperature. To 16 hours, TLC was performed to track the progress of the reaction (V 石油醚 :V 乙酸乙酯 =4:1) After the reaction is completed, dry and filter the filtrate, evaporate the filtrate to dryness under reduced pressure, and then pass through silica gel column chromatography (V 石油醚 :V 乙酸乙酯 =10:1) Purified to obtain 2.60 g of bromopaeonol as a white solid 2, Rf=0.28, yield 58.0%.

[0047] m.p.51.4~53.0℃; IR(KBr,cm -1 ):2956(-CH 3 ), 1651 (C=O), 1595, 1500, 1406, 1359, 1328, 1257, 1124, 1024, 837, 756, 646, 584, 522;

[0048] Therefore, the above compound 2 is 2-(4-bromobutoxy)-4-methoxyacetophenone, and its structu...

Embodiment 2

[0050] Example 2: Preparation of 6-Substituted Phenyl-5-cyano-2-thiouracil (Compound 4)

[0051] Add 0.01 mol of aromatic aldehyde, 0.01 mol of ethyl cyanoacetate, 0.01 mol of thiourea and 0.01 mol of potassium carbonate to 0.1 mol of absolute ethanol solution and reflux for 5-8 h, during which the reaction progress is detected by TLC; Precipitate in the form of precipitation, filter under reduced pressure, dissolve the precipitate in warm water, acidify it with acetic acid and re-precipitate, filter under reduced pressure, dry it, recrystallize from ethanol, and purify to obtain 6-substituted phenyl-5-cyano- 2-thiouracil;

[0052] Its structural formula is shown in the following formula, wherein, R 1 is aryl, H or CH 3 ;R 2 is CN or H; R 3 as OH or CH 3 ;

[0053]

[0054] The 4a is 6-(3-fluorophenyl)-5-cyano-2-thiouracil;

[0055] 4b is 6-phenyl-5-cyano-2-thiouracil;

[0056] 4c is 6-(2-fluorophenyl)-5-cyano-2-thiouracil;

[0057] 4d is 6-(3-hydroxyphenyl)-5-cyan...

Embodiment 3

[0065] Example 3: Preparation of 6-(3-Fluorophenyl)-5-cyano-4-hydroxy-2-paeonol mercaptopyrimidine (5a)

[0066] Get the 2-(4-bromobutoxy)-4-methoxyacetophenone 2 of 1mmol prepared in Example 1, be dissolved in the round-bottomed flask that 10mmol absolute ethanol is housed, add 1mmol of 6-( 3-Fluorophenyl)-5-cyano-2-thiouracil 4a, 1 mmol of anhydrous potassium carbonate was added, the temperature was raised to 78°C in a water bath, and the reaction was stirred at reflux for about 7 to 8 hours, during which TLC was performed to track the progress of the reaction (V 氯仿 :V 甲醇 =2:1) ​​After the reaction is completed, dry and filter, the filtrate is evaporated to dryness under reduced pressure and subjected to silica gel column chromatography (V 石油醚 :V 乙酸乙酯 =1:1) purification to obtain white solid 5a, yield 32.1%;

[0067] m.p.81.7~83.6℃; IR (KBr,cm -1 ): 2 947 (CH 3 ), 2 214(-CN), 1664(C=O), 1600, 1502, 1485, 1396, 1357, 1303, 1263, 1199, 1153, 1028, 999, 964, 796, 729, 646,...

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Abstract

The invention discloses a paeonol dihydropyrimidinone derivative as well as a preparation method and application thereof. The preparation method comprises the following steps: adding paeonol and a terminal dibromoalkane compound in an organic solvent and an acid binding agent to carry out Through a nucleophilic substitution reaction, brominated paeonol is generated; the aromatic aldehyde, ethyl cyanoacetate and thiourea are subjected to a cyclization reaction under an organic solvent and a catalyst to synthesize 6-substituted phenyl-5-cyano-2- thiouracil; finally, brominated paeonol and synthetic 6-substituted phenyl-5-cyano-2-thiouracil are substituted by nucleophilic under organic solvent and acid binding agent to synthesize paeonol Dihydropyrimidinone derivatives. The present invention provides a new class of paeonol dihydropyrimidinone derivatives, which have short preparation period, simple operation, low cost, and the obtained derivatives have high purity and stable quality; The introduction of a functional group dihydropyrimidinone on the phenol skeleton can improve the antitumor activity of the compound, which has further research significance.

Description

technical field [0001] The invention relates to ketone derivatives, in particular to a paeonol dihydropyrimidinone derivative and a preparation method and application thereof. Background technique [0002] Paeonol, also known as paeonol, paeonol, chemical name is 2-hydroxy-4-methoxyacetophenone, is a kind of skin from Ranunculaceae Paeonia moutan Sim. Natural product extracted from Pycnostelma paniculatum K. Schum). As the main active ingredient of Cortex Moutan, it has been widely studied for its anti-inflammatory, anti-tumor, anti-atherosclerotic, anti-diabetic, anti-mutagenic and anti-neuro-inflammatory activities. Paeonol has little toxicity and side effects, has a wide range of biological activities, and its simple structure also makes the structure modification process convenient and easy. With the continuous expansion of the synthesis of paeonol derivatives and their functions, it has been found that appropriate modification and transformation of their functional gr...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D239/28C07D239/38A61P35/00A61K31/505
CPCC07D239/28C07D239/38A61P35/00
Inventor 李芳耀庞富华黄琳马献力蒋彩娜李倩周小群
Owner GUILIN MEDICAL UNIVERSITY
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