3,5-bis(3-aminobenzylidene)-4-piperidone derivatives with antitumor activity and preparation method thereof

An aminobenzylidene, antitumor activity technology, applied in antitumor drugs, organic chemistry, drug combination and other directions, to achieve the effects of high synthesis yield, low toxicity and mild reaction conditions

Inactive Publication Date: 2016-06-15
BINZHOU MEDICAL COLLEGE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Also, Awasthia [5] Synthesized a series of butenedioic acid substituted 3,5-bis(2-chlorobenzylidene)-4-piperidone derivatives, and found t

Method used

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  • 3,5-bis(3-aminobenzylidene)-4-piperidone derivatives with antitumor activity and preparation method thereof
  • 3,5-bis(3-aminobenzylidene)-4-piperidone derivatives with antitumor activity and preparation method thereof
  • 3,5-bis(3-aminobenzylidene)-4-piperidone derivatives with antitumor activity and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0027] Synthesis of 3,5-bis(3-aminobenzylidene)-4-piperidinone (A)

[0028] Mix 0.01mol of 4-piperidone hydrochloride and 0.022mol of m-nitrobenzaldehyde in a solution of 25mL of ethanol and water, add dropwise 20mL of 20% sodium hydroxide solution at room temperature, stir and react at room temperature for 8 hours, pass through a thin layer Chromatography (TLC) thin layer analysis to determine the reaction endpoint. After the reaction was completed, it was suction filtered, and the obtained precipitate was washed with an appropriate amount of ether, and dried to obtain the intermediate as a light yellow powder. The intermediate and 0.06mol stannous chloride were added to 20mL of concentrated hydrochloric acid and stirred for 15h, the end point of the reaction was determined by thin-layer chromatography (TLC) analysis, the precipitate was suction filtered, 10% sodium carbonate solution lotion, 20mL ethanol / water ( Volume ratio 1:1) recrystallization to obtain a yellow powder,...

Embodiment 2

[0031] Synthesis of N-methyl-3,5-bis(3-aminobenzylidene)-4-piperidone (B)

[0032] Mix 0.01mol of N-methylpiperidone and 0.024mol of m-nitrobenzaldehyde in a solution of 20mL of methanol and water, add 25mL of 10% sodium hydroxide solution at room temperature, stir and react at room temperature for 12h, and pass thin-layer chromatography Thin layer analysis (TLC) was used to determine the end point of the reaction. The precipitate was suction filtered to obtain light yellow powder. Add the light yellow powder and 0.066mol tin protochloride to 25mL concentrated hydrochloric acid and stir for 6h, determine the end point of the reaction by thin layer chromatography (TLC) analysis, precipitate and suction filter, 10% sodium carbonate solution lotion, 25mL ethanol / water (volume ratio 1.5:1) recrystallization to obtain a yellow powder, namely N-methyl-3,5-bis(3-aminobenzylidene)-4-piperidone (B), 2.17g, yield 68 %.

[0033] IR (cm -1 ):3355(w),3347(w),3222(w),1600(s),1583(s),145...

Embodiment 3

[0035] Preparation method of 3,5-bis(3-aminobenzylidene)-4-piperidone with antitumor activity

[0036] Step 1: Preparation of 3,5-bis(3-nitrobenzylidene)-4-piperidone intermediate

[0037] Use m-nitrobenzaldehyde and 4-piperidone hydrochloride as raw materials, mix them in an alcoholic aqueous solution, add a catalyst, stir and react at room temperature for 4 hours, precipitate and filter to obtain an intermediate, which is directly used in the next reaction;

[0038] The molar ratio of m-nitrobenzaldehyde and 4-piperidone hydrochloride is greater than or equal to 2:1; the alcohol in the alcohol aqueous solution is isopropanol; the catalyst is potassium hydroxide solution with a mass concentration of 8% ;

[0039] Step 2: Preparation of 3,5-bis(3-aminobenzylidene)-4-piperidone derivative A

[0040] Perform reduction reaction with stannous chloride, concentrated hydrochloric acid and the intermediate obtained in step 1 for 18 hours, adjust the pH value to be greater than 12, ...

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Abstract

The invention relates to two 3,5-bis(3-aminophenyl)methylene-4-piperidone compounds with antitumor activity and a preparation method thereof, and belongs to the technical field of antitumor drugs and preparation methods thereof.The preparation method of the compounds includes the steps that 4-piperidone and m-nitrobenzaldehyde are subjected to a Clayson-Schmidt condensation reaction to obtain an intermediate, and then the intermediate is subjected to reduction with a reducing agent to obtain the products A and B.The compounds are good in antitumor activity, can avoid the genotoxicity of antitumor drugs used at present and have little toxicity on normal cells.The preparation method is easy and convenient to implement, reaction conditions are mild, the synthesis yield is high, and thus the preparation method can be widely popularized in the antitumor field easily.

Description

technical field [0001] The invention relates to two 3,5-bis(3-aminobenzylidene)-4-piperidone compounds with antitumor activity and a preparation method thereof, and belongs to the technical field of antitumor drugs and preparation methods thereof. Background technique [0002] The α,β-unsaturated ketone structural unit is the effective pharmacophore of the curcumin analogue 3,5-diarylmethylene-4-piperidone, which is a class of effective cytotoxic compounds discovered in recent years. The sulfhydryl group that does not exist in the nucleic acid has a better affinity, but has a lower affinity for the amino group, hydroxyl group and other groups that exist in the nucleic acid, showing obvious affinity selectivity, so it has attracted extensive attention from scholars. [1 , 2] . The pharmacophore of 3,5-diarylmethylene-4-piperidinone compounds is two α,β-unsaturated ketone units, which can form two consecutive alkylations on sulfhydryl groups. The main binding site for tumor...

Claims

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Application Information

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IPC IPC(8): C07D213/68A61P35/00A61P35/02
CPCC07D213/68
Inventor 侯桂革王春华孙居锋陈琴李宁
Owner BINZHOU MEDICAL COLLEGE
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