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Imidazo [4, 5-d] pyrimidone tricyclic derivative and anti-tumor application

A technology of pyrimidinone tricyclics and derivatives, applied in antitumor drugs, drug combinations, organic chemistry and other directions

Pending Publication Date: 2022-03-01
XINJIANG TECHN INST OF PHYSICS & CHEM CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, current treatments are limited by side effects and drug resistance, so finding new, safer anticancer drugs is critical

Method used

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  • Imidazo [4, 5-d] pyrimidone tricyclic derivative and anti-tumor application
  • Imidazo [4, 5-d] pyrimidone tricyclic derivative and anti-tumor application
  • Imidazo [4, 5-d] pyrimidone tricyclic derivative and anti-tumor application

Examples

Experimental program
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Effect test

Embodiment 1

[0069] Preparation of Compound A:

[0070] At a temperature of 0°C, 10.6 mL of ethyl cyanoacetate, 0.1 mol, and 45 mL of 45% acetic acid aqueous solution were stirred for 10 min, and 21.0 g, 0.3 mol of sodium nitrite was added in 3 times within one and a half hours, and reacted at room temperature for 5 h. The solvent was removed under reduced pressure and dried to give A as a yellow solid.

Embodiment 2

[0072] Preparation of Compound B:

[0073] Dissolve 10 g of the yellow solid A obtained in Example 1, 0.07 mmol, in 60 mL of water, slowly add 30 mL of saturated sodium bicarbonate solution, and add 34 g of sodium dithionite in 3 times at a temperature of 20°C within half an hour. After reacting for 2 hours, use di Extract with methyl chloride, dry the organic phase over anhydrous sodium sulfate, and remove the solvent under reduced pressure to obtain yellow oil B.

Embodiment 3

[0075] Preparation of Compound C:

[0076] The yellow oil B4.72g, 0.037mmol and 6.76g, 0.046mmol of triethyl orthoacetate obtained in Example 2 were heated to reflux in 30mL of acetonitrile for 1h, after cooling to room temperature, amine was added, stirred overnight, and the solid C obtained by filtration was :

[0077] Compound c1 is ethyl 5-amino-1-phenyl-1H-imidazole-4-carboxylate;

[0078] Compound c2 is ethyl 5-amino-1-(p-tolyl)-1H-imidazole-4-carboxylate;

[0079] Compound c3 is ethyl 5-amino-1-(p-ethylphenyl)-1H-imidazole-4-carboxylate;

[0080] Compound c4 is ethyl 5-amino-1-(p-methoxyphenyl)-1H-imidazole-4-carboxylate;

[0081] Compound c5 is ethyl 5-amino-1-(p-fluorophenyl)-1H-imidazole-4-carboxylate;

[0082] Compound c6 is ethyl 5-amino-1-(p-bromophenyl)-1H-imidazole-4-carboxylate;

[0083] Compound c7 is ethyl 5-amino-1-(p-chlorophenyl)-1H-imidazole-4-carboxylate;

[0084] Compound c8 is ethyl 5-amino-1-(m-chlorophenyl)-1H-imidazole-4-carboxylate;

[0085]...

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Abstract

The invention relates to an imidazo [4, 5-d] pyrimidone tricyclic derivative and an anti-tumor application thereof. The preparation method comprises the following steps: by taking ethyl cyanoacetate as an initial raw material, reacting with sodium nitrite in an acetic acid aqueous solution to obtain ethyl cyanohydroxyimino acetate, and then reducing by using sodium hydrosulfite in a saturated sodium bicarbonate solution to obtain 2-amino-2-ethyl cyanoacetate; the preparation method comprises the following steps: taking 4-aminoimidazole-5-carboxylic acid as a raw material, reacting with proper amine and triethyl orthoformate to obtain 3-position different substituted 4-aminoimidazole-5-carboxylic acid ethyl ester, and finally respectively reacting with delta-valerolactam and epsilon-caprolactam under the catalysis of phosphorus oxychloride to obtain condensed imidazo [4, 5-d] pyrimidone tricyclic derivatives (d1-d18 and e1-e13). The inhibition effects of 31 compounds on HT-29 human colon cancer cells, MCF-7 breast cancer cells and HeLa human cervical cancer cells are respectively investigated. Results show that doxycycline is used as a positive control drug, and activity screening results show that the five compounds have certain inhibitory activity on HT-29 human colon cancer cells; the four compounds have certain inhibitory activity on MCF-7 human breast cancer cells; the 17 compounds have certain inhibitory activity on HeLa human cervical cancer cells.

Description

technical field [0001] The present invention relates to an imidazo[4,5-d]pyrimidinone tricyclic derivative and its anti-tumor application. Through in vitro activity screening, it is found that 5 compounds have certain inhibitory activity on HT-29 human colon cancer cells; 4 1 compound has a certain inhibitory activity on MCF-7 human breast cancer cells; 17 compounds have a certain inhibitory activity on HeLa human cervical cancer cells. Background technique [0002] The International Agency for Research on Cancer released GLOBOCAN2020, the latest estimates of cancer incidence and mortality, and noted 19.3 million new cancer cases and nearly 10 million cancer deaths worldwide The hallmark of cancer is uncontrolled Abnormal cell growth, sometimes metastasizing, remains one of the leading causes of death worldwide. However, current treatments are limited by side effects and drug resistance, so finding new, safer anticancer drugs is critical. [0003] Heterocyclic compounds ar...

Claims

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Application Information

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IPC IPC(8): C07D487/14C07D471/14A61P35/00
CPCC07D487/14C07D471/14A61P35/00
Inventor 赵江瑜郭红梅聂礼飞阿吉艾克拜尔·艾萨
Owner XINJIANG TECHN INST OF PHYSICS & CHEM CHINESE ACAD OF SCI
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