A kind of microtubule polymerization inhibitor containing pyrazoline structure and its application

A technology of pyrazolines and structural formulas, applied in the preparation of anti-tumor drugs, in the field of new microtubule polymerization inhibitors, can solve the problems of large toxic and side effects, poor curative effect of solid tumors, multi-drug resistance, etc.

Active Publication Date: 2021-11-16
NANJING UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although the chemical structures and mechanisms of action of anti-tumor drugs are various, the anti-tumor drugs commonly used in clinical practice generally have many shortcomings such as poor curative effect on solid tumors, large toxic and side effects, and easy multidrug resistance.

Method used

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  • A kind of microtubule polymerization inhibitor containing pyrazoline structure and its application
  • A kind of microtubule polymerization inhibitor containing pyrazoline structure and its application
  • A kind of microtubule polymerization inhibitor containing pyrazoline structure and its application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0058] Example 1: 3-phenyl-5-(3,4,5-trimethoxyphenyl)-4,5-dihydro-1H-pyrazole-1-carboxylic acid methyl ester (I 1 ) preparation

[0059] The synthesis steps are: ① 3,4,5-trimethoxybenzaldehyde (392mg, 2.0mmol) and acetophenone (240mg, 2.0mmol) were dissolved in 20mL of absolute ethanol, KOH (6mmol, 336mg) was added, stirred at room temperature, and reacted After 24 hours, a solid substance was precipitated, suction filtered, washed, and recrystallized to obtain the intermediate product II 1 ; ② intermediate product II 1 (596 mg, 2.0 mmol) and 1 mL of 80% hydrazine hydrate solution were dissolved in 5 mL of isopropanol solution, and stirred and refluxed for 3 hours under nitrogen protection. After the temperature of the reaction solution dropped to room temperature, it was transferred to cold hydrazine, stirred at -20°C until a large amount of solids were precipitated, filtered under reduced pressure in a vacuum, and the solids were quickly washed three times with saturated s...

Embodiment 2

[0060] Example 2: 3-(3-methoxyphenyl)-5-(3,4,5-trimethoxyphenyl)-4,5-dihydro-1H-pyrazole-1-carboxylic acid methyl ester (I 5 ) preparation

[0061] For the synthesis method, refer to Example 1. Obtain white powder, productive rate 61.2%, melting point 164-166 ℃, nuclear magnetic spectrum is characterized as 1 H-NMR (DMSO-d 6 , 600MHz) δ7.39-7.30(m, 2H), 7.26(s, 1H), 7.04-7.02(m, 1H), 6.49(s, 2H), 5.39(dd, J=11.9, 5.4Hz, 1H) , 3.87-3.78 (m, 4H), 3.73 (s, 6H), 3.67 (s, 3H), 3.63 (s, 3H), 3.18 (dd, J=17.9, 5.5Hz, 1H).

Embodiment 3

[0062] Example three: 3-(3-hydroxyphenyl)-5-(3,4,5-trimethoxyphenyl)-4,5-dihydro-1H-pyrazole-1-carboxylic acid methyl ester (I 13 ) preparation

[0063] For the synthesis method, refer to Example 1. Obtain white powder, productive rate 77.1%, melting point 137-139 ℃, nuclear magnetic spectrum is characterized as 1 H-NMR (DMSO-d 6 , 600MHz) δ9.63(s, 1H), 7.25-7.20(m, 2H), 7.12(d, J=7.6Hz, 1H), 6.85(d, J=7.6Hz, 1H), 6.48(s, 2H ), 5.37(dd, J=11.8, 5.4Hz, 1H), 3.79(dd, J=17.8, 11.9Hz, 1H), 3.73(s, 6H), 3.66(s, 3H), 3.63(s, 3H) , 3.10 (dd, J=17.8, 5.3Hz, 1H).

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Abstract

The invention relates to the field of medicine, in particular to the use of a novel tubulin polymerization inhibitor (general formula I) containing a pyrazoline structure in the preparation of antitumor drugs.

Description

technical field [0001] The invention belongs to the fields of medicinal chemistry and medicine, and specifically relates to a novel microtubule polymerization inhibitor containing a pyrazoline structure, and also relates to a pharmaceutical composition of the derivative and its application in the preparation of antitumor drugs. Background technique [0002] In recent years, tumors, especially malignant tumors, have become one of the diseases that seriously threaten human health. Among the more than 5 billion people in the world, an average of 6.9 million people die from malignant tumors each year, and 8.7 million new cases are reported, and the number is constantly increasing. Methods such as chemotherapy, radiotherapy, surgery, biological therapy and Chinese and Western medicine have become the most effective methods for treating tumors. With the development of tumor drugs, new anti-tumor drugs are constantly being updated, which have played a huge role in improving the cu...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D231/06A61P35/00A61K31/415
CPCA61P35/00C07D231/06
Inventor 朱海亮张雅亮夏林颖杨蓉
Owner NANJING UNIV
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