Method for synthesizing EZH2 methyltransferase inhibitor GSK126

A technology of methyltransferase and synthetic method, which is applied in the field of drug synthesis and can solve the problems of time-consuming, long-term and high-cost

Active Publication Date: 2016-05-04
CHANGZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0008] In order to overcome the time-consuming and high-cost defects in the above-mentioned prior art, the present invention proposes a new synthetic method for improving GSK126

Method used

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  • Method for synthesizing EZH2 methyltransferase inhibitor GSK126
  • Method for synthesizing EZH2 methyltransferase inhibitor GSK126

Examples

Experimental program
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Embodiment 1

[0032]Example 1: 50g (0.18mmol) 2,5-dibromobenzoic acid was added to concentrated sulfuric acid. In order to make the 2,5-dibromobenzoic acid evenly distributed, the reaction system needs to be stirred for a period of time, and then passed through the constant pressure funnel Slowly add 62.5mL of concentrated nitric acid to keep the temperature below 70°C; after adding nitric acid, the reactants are stirred rapidly and heated to 100°C for 5 hours. The cooled reaction system was added to 2L of ice, and solids precipitated after adding to the ice. The white solid produced was filtered off with a Buchner funnel and washed several times with water; the solid was dissolved in 150 mL of glacial acetic acid and recrystallized to give the product 24.24 g (41% yield). 1 HNMR (CDCl 3 ,300MHz):δ8.65(d,J=2.36Hz,1H),8.74(d,J=2.36Hz,1H),12.60(s,1H); 13 CNMR (CDCl 3 ,75MHz): δ118.8, 122.9, 131.1, 134.9, 142.1, 152.5, 169.3.

Embodiment 2

[0033] Example 2: Other conditions are the same as Example 1, the reaction temperature is changed from 70°C to 60°C, and the yield of the product obtained is 43%.

Embodiment 3

[0034] Embodiment 3: Other conditions are the same as in Embodiment 1, the reaction temperature is changed to 130° C., and the yield of the product obtained is 40%.

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Abstract

The invention relates to a method for synthesizing an EZH2 methyltransferase inhibitor GSK126, and belongs to the field of medicinal chemistry. EZH2 is highly expressed in various malignant tumors and is expected to provide a new target for tumor therapy; GSK126 can effectively inhibit the activity of an EZH2 methyltransferase, thereby arousing the interest of people in research. According to the method provided by the invention, the reaction steps are simplified, and by using a chiral introduction method, the chiral separation link in the literature is avoided, and the synthesizing cost is reduced.

Description

technical field [0001] The invention relates to a new synthesis method of GSK126 which provides good prospects for the treatment of mutant lymphoma, and belongs to the field of drug synthesis. Background technique [0002] GSK126: (S)-6-Bromo-1-(isobutyl)-nitrogen-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3yl)methyl)-3 -Methyl-6-(6-(p-diazahexane-2-yl)piperidin-2-yl)-1-hydro-indole-4-carboxamide, CAS No. 1346574-57-9, molecular formula C 31 h 38 N 6 o 2 , molecular weight 526.67. Studies in recent years have shown that human malignant tumors are closely related to the abnormal expression of polycombgroup (PcG) proteins, especially polycombrepressivecomplex1 (PRC1) protein complexes and PRC2 protein complexes. The catalytically active subunit of PRC2 complex is Zeste gene enhancer homologue 2 (enhancerofzestehomolog2, referred to as EZH2). EZH2 is homologous to the Drosophila gene and is a core member of the PcG gene family. It is located on chromosome 7q35 and catalyzes ...

Claims

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Application Information

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IPC IPC(8): C07D401/14
CPCC07B2200/07C07D401/14
Inventor 陈新陆晨
Owner CHANGZHOU UNIV
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