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Tert-butyl substituted asymmetrical piperidone compounds with anti-tumor activities and preparation method thereof

A technology of anti-tumor activity and piperidone, which is applied in anti-tumor drugs, organic chemistry, drug combination, etc., can solve the problems of few reports on asymmetric derivatives, and achieve genotoxicity avoidance, low toxicity, and high synthesis yield Effect

Inactive Publication Date: 2016-06-08
BINZHOU MEDICAL COLLEGE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Nevertheless, the compounds reported in the literature and previously synthesized by our research group are all symmetrical 3,5-bis(arylene)-4-piperidinone derivatives, and there are few reports on asymmetric derivatives with different substituents on both sides.

Method used

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  • Tert-butyl substituted asymmetrical piperidone compounds with anti-tumor activities and preparation method thereof
  • Tert-butyl substituted asymmetrical piperidone compounds with anti-tumor activities and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0024] Synthesis of 3-(4-tert-butylbenzylidene)-5-(2-methoxybenzylidene)-4-piperidone (A)

[0025] Mix 0.01mol of N-methyl-4-piperidone with 0.01mol of 4-tert-butylbenzaldehyde and 0.01mol of 2-methoxybenzaldehyde in a solution of 25mL of ethanol and water, and add dropwise at room temperature 15 mL of 20% sodium hydroxide solution was stirred at room temperature for 4 h, and the end point of the reaction was determined by thin-layer chromatography (TLC) analysis. After the reaction, the obtained oil was chromatographed on a 200-300 mesh silica gel column (eluent: petroleum ether / ethyl acetate = 3:1) to obtain a yellow oil, which was the inventive product 3-(4-tert-butylbenzylidene yl)-5-(2-methoxybenzylidene)-4-piperidone (A), 2.23 g, the yield is 61%.

[0026] 1 HNMR (400MHz, CDCl 3 )δ8.06(s, 1H, -C=CH), 7.80(s, 1H, -C=CH), 7.44(d, J=7.5Hz, 2H, -C 6 h 4 ),7.36(m,3H,-C 6 h 4 ),7.20(d,J=7.4Hz,1H,-C 6 h 4 ),6.97(t,J=7.6Hz,1H,-C 6 h 4 ),6.93(d,J=8.4Hz,1H,-C 6 h 4 ),...

Embodiment 2

[0028] Synthesis of 3-(4-tert-butylbenzylidene)-5-(4-methoxybenzylidene)-4-piperidone (B)

[0029] Mix 0.01mol of N-methyl-4-piperidone with 0.011mol of 4-tert-butylbenzaldehyde and 0.010mol of 4-methoxybenzaldehyde in a solution of 16mL of methanol and water, add dropwise at room temperature 15 mL of 10% potassium hydroxide solution was stirred at 40° C. for 3 h, and the end point of the reaction was determined by thin layer chromatography (TLC) analysis. After the reaction, the precipitate was filtered with suction, and the resulting precipitate was chromatographed on a 200-300 mesh silica gel column (eluent: petroleum ether / ethyl acetate = 4:1) to obtain a bright yellow powder, which is the inventive product 3-(4-tert-butyl Benzylidene)-5-(4-methoxybenzylidene)-4-piperidone (B), 2.32 g, yield 62%.

[0030] Mp:154~156℃.IR(cm -1 ):2954(s), 2783(m), 1675(m), 1604(s), 1505(s), 1456(s), 1253(s), 1166(s), 1031(s), 918(s) ),830(s). 1 HNMR (400MHz, CDCl 3 )δ7.78(d,2H,-C=CH),7....

Embodiment 3

[0032] Synthesis of 3-(4-tert-butylbenzylidene)-5-(3,4-dimethoxybenzylidene)-4-piperidone (C)

[0033] Mix 0.01mol of N-methyl-4-piperidone with 0.009mol of 4-tert-butylbenzaldehyde and 0.011mol of 3,4-dimethoxybenzaldehyde in 20mL of propanol and water solution, room temperature 15 mL of 10% sodium hydroxide solution was added dropwise, stirred at 50° C. for 3.5 h, and the end point of the reaction was determined by thin layer chromatography (TLC) analysis. After the reaction was completed, the precipitate was filtered by suction, and the resulting precipitate was chromatographed on a 300-400 mesh silica gel column (eluent: petroleum ether / ethyl acetate = 4:1) to obtain a yellow powder, which is the inventive product 3-(4-tert-butylbenzene Methylene)-5-(3,4-dimethoxybenzylidene)-4-piperidone (C), 2.3 g, yield 57%.

[0034] Mp:155~157℃.IR(cm -1 ):2956(s), 2837(m), 1670(m), 1609(s), 1515(s), 1460(s), 1325(s), 1253(s), 1142(s), 1024(s) ),990(m),927(s),855(s),766(m). 1 HNMR (...

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Abstract

The invention relates to six tert-butyl substituted asymmetrical piperidone compounds with anti-tumor activities and a preparation method thereof, and belongs to the technical field of anti-tumor medicaments and a preparation method thereof. According to the preparation method, a Claisen-Schmidt condensation reaction is performed on N-methyl-4-piperidone, 4-tert-butylbenzaldehyde and another aromatic aldehyde to obtain products A-F. The compounds have high anti-tumor activities, genotoxicity of the conventional anti-tumor medicaments can be avoided, and the toxicity to normal cells is low. The preparation method is easy and convenient to operate, is mild in the reaction condition, is high in synthesis yield, and can be widely popularized in the anti-tumor field.

Description

technical field [0001] The invention relates to a series of tert-butyl substituted asymmetric piperidone compounds with antitumor activity and a preparation method thereof, belonging to the technical field of antitumor drugs and preparation methods thereof. Background technique [0002] 3,5-diaryl methylene-4-piperidone derivatives belong to curcumin analogs, which contain two α,β-unsaturated ketone pharmacophores, which can inhibit the higher content of tumor cells Sulfhydryl has a strong affinity, thus exhibiting superior antitumor activity [1] . Compared with clinical anti-tumor drugs, it has two advantages: first, as a cytotoxic drug, it can effectively avoid the genotoxicity of current clinical chemotherapy drugs, and the experimental verification that the mechanism of cell apoptosis may be through the activation of caspase3 to induce internucleosomal DNA It is also confirmed by experiments that it induces cell autophagy; the second is that the molecule contains two α...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D213/68A61P35/00A61P35/02
CPCC07D213/68
Inventor 侯桂革王春华孙居锋李宁陈琴燕珂
Owner BINZHOU MEDICAL COLLEGE
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