An anthranilamide compound based on entinotine skeleton and its preparation and application

A technology of aminobenzamide and entinostat, which is applied in the field of medicine and can solve problems such as neutropenia and leukopenia

Active Publication Date: 2022-07-05
NANHUA UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the targets of CDK inhibitors on the market are all CDK4 / 6, which are all aimed at breast cancer, and they have adverse reactions such as neutropenia and leukopenia

Method used

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  • An anthranilamide compound based on entinotine skeleton and its preparation and application
  • An anthranilamide compound based on entinotine skeleton and its preparation and application
  • An anthranilamide compound based on entinotine skeleton and its preparation and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] pyridin-3-ylmethyl 4-(2-aminobenzamido)benzylcarbamate (compound X5, formula II, m=1, X=N)

[0027] (1) Add 3-pyridinemethanol (Formula 6, X=N, 10 mmol), N,N'-carbonyldiimidazole (CDI, 11 mmol) and tetrahydrofuran (50 mL) to a 100 mL reaction flask, and react at room temperature for 1 h. 4-Aminobenzylamine (11 mmol), 1,8-diazabicycloundec-7-ene (DBU, 10 mmol) and triethylamine (15 mmol) were added and reacted at room temperature for 6 h. After the completion of the reaction monitored by TLC, the solvent was evaporated by rotary evaporation, and the product pyridin-3-ylmethyl 4-aminobenzylcarbamate (formula 7, m=1, X=N) was obtained by column chromatography in a yield of 90%.

[0028] (2) pyridin-3-ylmethyl 4-aminobenzylcarbamate (1 mmol), 2-((tert-butoxycarbonyl)amino)benzoic acid (1.2 mmol) 1-ethyl-(3-dimethylaminopropyl)carbonyl Diimine hydrochloride (EDCl, 1.2 mmol), 1-hydroxybenzotriazole (HOBt, 1.3 mmol) were placed in a 50 ml round bottom flask and replaced with...

Embodiment 2

[0031] pyridin-3-ylmethyl 4-(2-(methylamino)benzamido)benzylcarbamate (compound X6, formula II, m=1, X=N, R 2 =NHCH 3 )

[0032] (1) Add 3-pyridinemethanol (Formula 6, X=N, 10 mmol), N,N'-carbonyldiimidazole (CDI, 11 mmol) and tetrahydrofuran (50 mL) to a 100 mL reaction flask, and react at room temperature for 1 h. 4-Aminobenzylamine (11 mmol), 1,8-diazabicycloundec-7-ene (DBU, 10 mmol) and triethylamine (15 mmol) were added and reacted at room temperature for 6 h. After the completion of the reaction monitored by TLC, the solvent was evaporated by rotary evaporation, and the product pyridin-3-ylmethyl 4-aminobenzylcarbamate (formula 7, m=1, X=N) was obtained by column chromatography in a yield of 90%.

[0033] (2) pyridin-3-ylmethyl 4-aminobenzylcarbamate (1 mmol), N-methylanthracene (1.2 mmol), 1-ethyl-(3-dimethylaminopropyl) carbamide hydrochloride (EDCl, 1.2 mmol), 1-hydroxybenzotriazole (HOBt, 1.3 mmol) was placed in a 50 ml round bottom flask and replaced with argon...

Embodiment 3

[0035] pyridin-3-ylmethyl 4-(2-(dimethylamino)benzamido)benzylcarbamate (compound X7, formula II, m=1, X=N, R 2 =N(CH 3 ) 2 )

[0036] The raw material N-methylanthracene in step (2) of Example 2 was replaced with 2-(dimethylamino)benzoic acid, and the remaining steps were prepared in the same manner as in Example 2, and the yield was 55%. 1 H NMR (300 MHz, Acetone- d 6 ) δ 12.04 (s, 1H), 8.64 (s, 1H), 8.54 (d, J = 3.8 Hz, 1H), 8.10 (dd, J = 7.8, 1.7 Hz, 1H), 7.82 (d, J =7.8 Hz, 1H), 7.74 (d, J = 8.5 Hz, 2H), 7.56 – 7.48 (m, 1H), 7.46 – 7.35 (m, 2H), 7.31 (d, J = 8.4 Hz, 2H), 7.27 – 7.20 (m, 1H), 6.96 (s, 1H), 5.16 (s, 2H), 4.33 (d, J = 6.2 Hz, 2H), 2.85 (s, 6H). 13 C NMR (75 MHz, Acetone- d 6 ) δ164.82, 157.14, 153.29, 149.85, 149.66, 139.17, 136.70, 135.61, 134.11,133.09, 131.80, 128.79, 128.72, 124.89, 124.38, 121.20, 120.52, 120.42,64.25, 45.28, 44.82.

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Abstract

The invention provides an anthranilamide compound based on entinot skeleton and its preparation and application. The structural formula of the anthranilamide compounds based on the entinotine skeleton prepared by the present invention is wherein, R is methylamino, dimethylamino, hydroxyl, NH 2 or; X=C,N; m=0,1. The anthranilamide compound has the effect of inhibiting the proliferation of gastric cancer cells as determined by MTT method, has significant anti-gastric cancer activity, has higher activity than 5-fluorouracil at the cellular level, and has lower toxicity, and can be used for the preparation of anti-gastric cancer drugs .

Description

technical field [0001] The invention belongs to the technical field of medicine, in particular to an anthranilamide compound based on entinot skeleton and a preparation method thereof, and also relates to the application of the compound in the preparation of an anti-gastric cancer drug. Background technique [0002] Tumor is the second largest killer that seriously threatens human life and health after cardiovascular and cerebrovascular diseases. In 2018, there were 18.1 million new cases of cancer worldwide and 9.6 million deaths. Among them, the incidence of gastric cancer ranks fifth, and the mortality rate ranks third. According to statistics, in 2018, there were 1.03 million new cases of gastric cancer and 783,000 deaths worldwide, which is equivalent to 1 in every 12 deaths caused by malignant tumors in the world. As a large country with gastric cancer, China's annual gastric cancer deaths account for more than 40% of the total gastric cancer deaths in the world duri...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D213/30C07C271/20C07C271/28C07C269/00C07C269/06A61P35/00
CPCC07D213/30C07C271/20C07C271/28C07C269/00C07C269/06A61P35/00Y02A50/30
Inventor 王震石桃张红花卢莹美冯益悦李俊芳
Owner NANHUA UNIV
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