O-dicyano-acenaphtho pyrazine compound and anti-tumor application thereof

A compound, adjacent two technology, applied in antitumor drugs, organic chemistry, drug combination and other directions, can solve the problems of low solubility, difficult testing, low yield and so on

Inactive Publication Date: 2010-06-09
DALIAN UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, both have disadvantages such as low yield, isomers, difficult separation, instability, low solubility, and difficult testing.

Method used

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  • O-dicyano-acenaphtho pyrazine compound and anti-tumor application thereof
  • O-dicyano-acenaphtho pyrazine compound and anti-tumor application thereof
  • O-dicyano-acenaphtho pyrazine compound and anti-tumor application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036] Embodiment 1: the synthesis of 5-bromoacenaphthenequinone (2)

[0037] In a 500mL two-necked flask, add 20g (109.8mmol) of acenaphthylquinone and 25.0mL of liquid bromine (466.8mmol), start stirring, control the temperature in an oil bath at 60-70°C, and reflux the reaction solution. After 2 hours, stop the reaction and add Sodium bisulfate aqueous solution until the reaction solution is colorless. After diluting with water, filter under reduced pressure, and wash with water for several times for beating until pH=7.0. The filter cake was recrystallized four times in glacial acetic acid to obtain 5-bromoacenaphthoquinone as brown-yellow needle-like crystals with a yield of 90%.

[0038] 1 H NMR (400MHz, DMSO) δ (ppm) 8.39(d, 1H), 8.21(d, 1H), 8.15(d, 1H), 8.04(t, 1H), 7.96(d, 1H).

Embodiment 2

[0039] Example 2: Synthesis of 3-bromo-acenaphthopyrazine-8,9 dinitrile (3)

[0040] Add 200mg (0.77mmol) of 5-bromoacenaphthylquinone and 110mg (1.07mmol) of diaminomaleonitrile into a 15ml two-necked flask, then add 10ml of glacial acetic acid, stir and heat under reflux for 2.0h, pour into water after cooling, filter, and dry use CH 2 Cl 2 : Petroleum ether=3: 1 (volume ratio) solution is that eluent carries out separation and purification on silica gel column, obtains bright yellow 3-bromo-acenaphthopyrazine-8, 9 dinitriles 192mg (0.58mmol), yield 67.7%.

[0041] 1 H NMR (400MHz, CDCl 3)δ (ppm) 8.03-8.06(t, 1H), 8.18-8.19(d, 1H), 8.34-8.35(d, 1H), 8.48-8.50(d, 1H), 8.56-8.57(d, 1H).

Embodiment 3

[0042] Example 3: Synthesis of 3-(2-dimethyl)ethylamino-acenaphthopyrazine-8,9 dinitrile (4a)

[0043] Take 100 mg (0.3 mmol) of 3-bromo-acenaphthopyrazine-8,9 dicarbonitrile in a 10 ml round bottom flask, add 5 ml of ethylene glycol monoether, and add 234 μl (2.0 mmol) of ethylene glycol monoether under stirring, N 2 Heated under protection and refluxed for 45min, the solution gradually changed from light yellow to dark red. After cooling, it was poured into water and filtered to obtain a red solid. After drying, dichloromethane:methanol:triethylamine=100:2.5:1 (volume ratio) as the eluent to carry out separation and purification on a silica gel column to obtain red powdery solid 3-(2-dimethyl) ethylamino-acenaphthopyrazine-8, 9 dinitrile 50mg (0.15mmol), yield 50.0%.

[0044] 1 H NMR (400MHz DMSO) δ (ppm) 8.78-8.76 (d, 1H), 8.54-8.52 (d, 1H), 8.36 (t, 1H), 8.31-8.29 (d, 1H), 7.89-8.91 (t, 1H), 6.93-6.95(d, 1H), 3.64-3.66(m, 2H), 2.84(t, 2H), 2.42(s, 6H); HRMS(EI) m / z(M+H...

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PUM

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Abstract

The invention relates to a DNA-targeted o-dicyano-acenaphtho pyrazine compound in the field of application of antineoplastic medicaments. The compound is prepared by taking acenaphthene quinone as a raw material and performing bromination, cyclization and aromatic nucleophilic substitution reaction. The compound is characterized in that: one end takes an amino straight chain of a flexible side chain or an annular group as an electron-donating group, while the other end takes two cyanogen groups as electron-withdrawing groups; the two ends form an electron deficient large-plane conjugated system; and the structure accords with an ideal DNA intercalator. The compound shows obvious inhibitory activity to an in vitro test of MCF-7 (human mammary cancer cells).

Description

technical field [0001] The invention relates to the design of acenaphthopyrazine compounds in the field of biochemical industry and their application to inhibit tumor cells. Background technique [0002] DNA is an important component of organisms, the carrier of genetic information and the material basis of gene expression, and plays a very important role in biological growth, development, reproduction and other life activities. Malignant tumors are new organisms formed by the abnormal proliferation of cells in local tissues under the action of various tumorigenic factors. Chemotherapeutic drugs targeting DNA can act on the DNA of tumor cells, thereby causing damage to DNA, triggering DNA-damage-repair mechanism responses, triggering cell cycle arrest or inducing cell apoptosis. [0003] Since the word intercalator was proposed by Lennna in 1961, a lot of research has been done on it. It refers to the reversible interaction between small molecular substances of polycyclic ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D241/38C07D401/12A61K31/498A61K31/5377A61K31/541A61P35/00
Inventor 崔京南邢俊岭王爽张志超高金吴桂叶金礼吉
Owner DALIAN UNIV OF TECH
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