Preparation method and application of N-substituted-3,5-dibenzal piperidine-4-one

A bisbenzylidene piperidine, phenyl technology, applied in the field of new anti-leukemia K562 cell proliferation drug lead compounds, can solve the problem of chronic myeloid leukemia being difficult to cure, and achieve obvious novelty and creativity, easy production, and remarkable practicality sexual effect

Inactive Publication Date: 2011-02-16
SHANGHAI NORMAL UNIVERSITY
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Chronic myelogenous leukemia is difficult to cure because there is no ideal drug that can effectively inhibit the proliferation of K562 cells in the existing technology

Method used

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  • Preparation method and application of N-substituted-3,5-dibenzal piperidine-4-one
  • Preparation method and application of N-substituted-3,5-dibenzal piperidine-4-one
  • Preparation method and application of N-substituted-3,5-dibenzal piperidine-4-one

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0050] Example 1: Preparation of (Ia) N-(4-methylbenzyl)-3,5-bisbenzylidenepiperidin-4-one.

[0051] At room temperature, add 0.16mol methyl acrylate and 7mL methanol into a 100mL three-necked flask, stir, and slowly add a mixture of 0.04mol p-methylbenzylamine and 4mL methanol into the three-necked flask, so that the temperature of the reaction system does not exceed 50 ℃. After the dropwise addition, heat to reflux for 8 hours. After the reaction is over, recover methanol and unreacted methyl acrylate, and distill under reduced pressure to obtain light yellow oily liquid N, N-bis(β-methyl propionate) p-methyl Benzylamine (2a).

[0052] Add 15mL of anhydrous toluene and 0.122mol of sodium metal to a 250mL dry three-necked flask, stir and heat to reflux, add 0.2mL of anhydrous methanol, and then slowly add 0.04mol of N,N-bis(β-propionate methyl ester) to A mixture of methylbenzylamine (2a) and 20mL of anhydrous toluene. After the dropwise addition was completed, it was refl...

Embodiment 2

[0055] Example 2: Preparation of (Ib) N-(4-methylbenzyl)-3,5-bis(4-methylbenzylidene)piperidin-4-one.

[0056] N-p-methylbenzylpiperidin-4-one (4a) obtained by the preparation method of Example 1, take N-p-methylbenzylpiperidin-4-one (4a) 0.005mmol and 0.01mol p-methylbenzylpiperidin-4-one Base benzaldehyde was mixed in a 50mL dry round bottom bottle, 15mL of absolute ethanol was added, and 1mL of 10% NaOH was added during stirring, and solids precipitated after 40min. After the reaction, the solid was washed with ethanol, and recrystallized with ethyl acetate and petroleum ether to obtain N-(4-methylbenzyl)-3,5-bis(4-methylbenzylidene)piperidine-4 - Ketones (Ib).

[0057] Yield: 82%; yellow solid, mp 170-171℃; 1 H NMR (400MHz, CDCl 3 )δ2.28(s, 3H), 2.36(s, 6H), 3.66(s, 2H), 3.83(s, 4H), 7.04(d, J=7.8Hz, 2H), 7.13(d, J=7.9 Hz, 2H), 7.17(d, J=8.0Hz, 4H), 7.25(d, J=8.1Hz, 4H), 7.76(s, 2H); IR (KBr): 2916, 2745, 1670, 1613, 1578 , 1558, 1264, 1180, 1072, 813em -1 ;Anal.calc...

Embodiment 3

[0058] Example 3: Preparation of (Ic) N-(4-methylbenzyl)-3,5-bis(4-methoxybenzylidene)piperidin-4-one.

[0059] N-p-methylbenzylpiperidin-4-one (4a) obtained by the preparation method of Example 1, take N-p-methylbenzylpiperidin-4-one (4a) 0.005mmol and 0.01mol p-methylbenzylpiperidin-4-one Oxybenzaldehyde was mixed in a 50mL round bottom bottle, 15mL of absolute ethanol was added, 1mL of 10% NaOH was added with stirring, and stirred at room temperature for 30min, a yellow solid was precipitated, and the reaction progress was tracked by thin layer chromatography (TLC). After the reaction is over, wash the solid with ethanol, and recrystallize with ethyl acetate and petroleum ether to obtain N-(4-methylbenzyl)-3,5-bis(4-methoxybenzylidene)piperidine- 4-keto (Ic).

[0060] Yield: 87%; yellow solid, mp 172-174℃; 1 H NMR (400MHz, CDCl 3 )δ2.28(s, 3H), 3.66(s, 2H), 3.84(s, 4H), 3.91(s, 6H), 7.04(d, J=7.8Hz, 2H), 7.13(d, J=7.9 Hz, 2H), 7.25(d, J=8.3Hz, 4H), 7.42(d, J=8.4Hz, 4H),...

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Abstract

The invention belongs to a lead compound of a novel drug for preventing leukaemia K562 cell proliferation and relates to a preparation method and application of N-substituted-3,5-dibenzal piperidine-4-one which can effectively inhibit leukaemia K562 cell proliferation. The preparation method comprises the following steps of: performing Michael addition reaction for substituted amine and methyl acrylate to prepare a yellow oily object N,N-di(beta-methyl propionate) substituted amine; performing Dieckmann condensation under effect of sodium alkoxide and performing hydrolysis and decarboxylationunder effect of acid to obtain a yellow oily object N-substituted piperidine-4-one; and dehydrating the product obtained to obtain the N-substituted-3,5-dibenzal piperidine-4-one with the general formula (I). The product of the invention has higher inhibition activity to eukaemia K562 cell proliferation and the method has the advantages of simple process and easy production.

Description

technical field [0001] The invention belongs to the leading compound of a new anti-leukemia K562 cell proliferation drug, in particular to the preparation of a class of N-substituted-3,5-bisbenzylidenepiperidin-4-one compounds capable of effectively inhibiting the proliferation of leukemia K562 cells and its application in Application in inhibiting the proliferative activity of leukemia K562 cells. Background technique [0002] Leukemia is one of the diseases with the highest mortality rate in the world today, which has caused serious harm to human health. The incidence of leukemia in my country ranks sixth among various tumors. Chronic leukemia is a leukemia with clinical onset and relatively slow development, which is divided into chronic myelogenous leukemia and chronic lymphocytic leukemia. Chronic myelogenous leukemia, referred to as chronic myelogenous leukemia (Chronic Myelognous Leukemia, CML), the cell line K562 in chronic myelogenous leukemia, because its own resi...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61P35/02A61K31/45A61K31/4525C07D213/68C07D405/14
Inventor 薛思佳王静倪振杰
Owner SHANGHAI NORMAL UNIVERSITY
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