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3-piperazinyl chalcone derivative, pharmaceutical composition and application thereof

A kichalcone and derivative technology, which can be applied in the directions of drug combination, antitumor drug, pharmaceutical formulation, etc., can solve the problems of poor pertinence and low activity, and achieve the effects of cheap raw materials, simple synthesis and good activity

Active Publication Date: 2020-10-02
EAST CHINA UNIV OF SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, natural chalcone molecules still have disadvantages such as lack of pertinence and generally low activity. Taking the chalcone structure as a structural model, after structural modification and transformation, it has been found that highly active molecules have been widely valued.

Method used

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  • 3-piperazinyl chalcone derivative, pharmaceutical composition and application thereof
  • 3-piperazinyl chalcone derivative, pharmaceutical composition and application thereof
  • 3-piperazinyl chalcone derivative, pharmaceutical composition and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] The preparation of 3-position piperazinyl chalcone derivatives MY1-MY2, its reaction formula is as follows:

[0034]

[0035] (1) Preparation of 3-(N-BOC) piperazine benzaldehyde acetal (intermediate S1)

[0036] Put Pd(OAc) into a dry 150mL three-neck flask 2 (24mg, 1mol%Pd), ligand BINAP (0.15mmol, 1.5mol%), NaO-t-Bu (1.34g, 14mmol), 20mL of toluene solvent that redistilled, then weigh the reaction raw material 3-bromobenzaldehyde Acetal 2.3g (10mmol), and 1-tert-butoxycarbonylpiperazine (12mmol) (must be put into the reaction mixture after NaO-t-Bu) were put into the reaction flask while using N 2 Protected, then slowly heated to 100 °C for 24 hours, then TLC detection, until the raw materials were reacted, then extracted with ethyl acetate 3 times, 80 mL each time, combined with organic solvents, washed with water and saturated brine in sequence, and the organic phase was washed with anhydrous sulfuric acid Sodium dry. After a few minutes, the organic solvent ...

Embodiment 2

[0046] Preparation of 4-Piperazinyl Chalcone Derivative YH1

[0047] Only the 3-bromobenzaldehyde acetal in Example 1 was replaced with 4-bromobenzaldehyde acetal, and other experimental conditions and methods remained unchanged, and finally the target compound 2',4'-dimethoxy -4-piperazinylchalcone YH1, the yield is 87%.

[0048] Compound YH1, yellow solid, 1 H NMR (400MHz, CDCl 3 )δ7.74(d, J=8.6Hz, 2H), 7.62(d, J=15.7Hz, 1H), 7.54(d, J=8.6Hz, 2H), 7.40(d, J=15.7Hz, 1H) ,6.91(d,J=8.6Hz,1H),6.57(dd,J=8.6,2.1Hz,1H),6.50(d,J=2.0Hz,1H),3.90(s,3H),3.87(s, 3H), 3.52(s,4H), 3.35(s,4H). HRMS(ESI): Calcd for C 21 h 24 N 2 o 3 [M+H] + 353.1865; Found 353.1861.

Embodiment 3

[0050] The preparation of 3-position piperazinyl chalcone derivative MY3, its reaction formula is as follows:

[0051]

[0052] (1) Preparation of 2,4,6-trihydroxyacetophenone (intermediate S5)

[0053] Weigh 10g (0.08mol) of phloroglucinol and place it in a reaction vessel, add 40mL of ethyl acetate to dissolve, then add 10mL of acetic anhydride, slowly add BF under stirring at room temperature 3 ·Et 2 O solution 8mL, then slowly heated to 40°C for reaction, 2mL of acetic anhydride was added every two hours during the first 6h of the reaction process, BF 3 ·Et 2 O solution 1mL, react for 10h to check that the raw materials have reacted completely. 150 mL of water was added to the reaction liquid, stirred, and the solvent was distilled off under reduced pressure, and a large amount of yellow solid was precipitated in the distillation bottle. The yellow solid was recrystallized with water, placed for crystallization, suction filtered, dried and weighed to obtain intermed...

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Abstract

The present invention relates to a 3-site piperazinylchalcone derivative, which has a structure formula represented by a general formula (I) defined in the specification, wherein R is one selected from a substituted or unsubstituted phenyl group, a fused ring group and substituted or a unsubstituted heterocyclic group. The present invention further provides a pharmaceutical composition of the3-site piperazinylchalcone derivative, and applications thereof. According to the present invention, the results of the activity test based on P-gp target show that the 3-site piperazinylchalcone derivative and the pharmaceutical composition have good activity, can provide practical value in the treatment of the multidrug resistance of tumors, can solve the technical problems of difficult synthesis and high cost in the synthesis of the reversing agent used in the prior art, and is meaningful.

Description

technical field [0001] The present invention relates to the field of medical technology, in particular to the field of pharmaceutical chemical synthesis, specifically a 3-position piperazinyl chalcone derivative, its pharmaceutical composition and its application. Background technique [0002] Malignant tumors are one of the major diseases that seriously threaten people's lives and health. Chemotherapy of tumors is still an indispensable means of tumor treatment, and cancer patients who receive long-term chemotherapy will develop multidrug resistance (multiple drug resistance) during the course of treatment. drug resistance, MDR). MDR refers to the cross-resistance of tumor cells to other anti-tumor drugs with different structures and mechanisms of action while developing resistance to one anti-tumor drug. The main cause of MDR is the efflux of anticancer drugs by P-glycoprotein (P-glycoprotein, P-gp), and other reasons include multidrug resistance-related protein (MRP), lu...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D295/112C07D311/04A61K31/496A61K31/495A61P35/00
CPCA61P35/00C07D295/112C07D311/04
Inventor 马磊刘建文唐赟尹欢欢董静静蔡迎春刘桂霞时夕蒙王皓
Owner EAST CHINA UNIV OF SCI & TECH
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