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2-phenylaminopurine plk1 (polo-like kinase 1) inhibitors and applications thereof

An amino and purine technology, applied in the field of Polo-like kinase 1 inhibitor, 2-phenylaminopurine derivatives, can solve the problems of tumor cell bipolar spindle formation obstruction, apoptosis, growth inhibition, etc.

Inactive Publication Date: 2013-11-27
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Importantly, the work of many scholars has shown that knocking down PLK1 in tumor cells with antisense technology, siRNA technology or small molecule inhibitors can cause the formation of bipolar spindles in tumor cells to be blocked, growth inhibition, and even apoptosis

Method used

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  • 2-phenylaminopurine plk1 (polo-like kinase 1) inhibitors and applications thereof
  • 2-phenylaminopurine plk1 (polo-like kinase 1) inhibitors and applications thereof
  • 2-phenylaminopurine plk1 (polo-like kinase 1) inhibitors and applications thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0089] 2-Chloro-9-cyclopentyl-9H-purine (M1)

[0090] Add 5g (25.8mmol) of 2,4-dichloro-5-nitropyrimidine and 2ml THF into a 50ml reaction bottle, stir evenly and cool to -40°C, slowly drop in 2.2g cyclopentylamine, react for 4h, and complete; Remove the solvent by steaming under pressure, add water, extract (50ml×3), column chromatography (DCM:MeOH=100:1), and obtain 4.26g of 2-chloro-4-(N-cyclopentyl)amino 5-nitropyrimidine, Yield 67.9%, MS [M+H] + 243.1.

[0091] Add 2-chloro-4-(N-cyclopentyl)amino 5-nitropyrimidine 9.1g (36.9mmol) and NH 4 Cl 10g (0.18mol), 70% ethanol aqueous solution 100ml, mechanically stirred, slowly added reduced iron powder 10.5g (0.19mol), reflux reaction for 5h. Suction filtration while hot, evaporate the solvent under reduced pressure, extract (50ml×3), and column chromatography (EA:PE=100:1) to obtain 2-chloro-4-(N-cyclopentyl)aminopyrimidine-5- Amine 7.6g, yield 95%, MS [M+H] + 213.1.

[0092] Add 1.04g (4.9mmol) of the compound 2-chloro-4...

Embodiment 2

[0094] 2-Chloro-9-isopropyl-9H-purine (M2)

[0095] The preparation method was similar to M1, and 0.80 g of the sample was obtained with a yield of 67.5%. MS[M+H] + 197.1, MS[M-H] - 195.1.

Embodiment 3

[0097] 4-(9-Cyclopentyl-9H-purin-2-ylamino)benzoic acid (M3)

[0098] Add 10.1g (0.45mmol) of M10.1g (0.45mmol) and 0.07g (0.42mmol) of ethyl p-aminobenzoate into a 25ml eggplant-shaped bottle, stir well, add an appropriate amount of ethylene glycol, and reflux for 24h. After cooling, the reaction solution was poured into a large amount of water, and left to stand, a white milky solid precipitated, which was filtered by suction and dried to obtain 34 mg of a white solid, with a yield of 21.3%.

[0099] Add 0.25g (0.71mmol) of the product from the previous step, 0.08g (2mmol) of KOH, and 10ml of MeOH into a 25ml eggplant-shaped flask, and reflux for 12h. Add 10ml H 2 O, the pH was adjusted to be acidic, and a solid was precipitated. After drying, 0.23 g of a brown solid was obtained, and the yield was 98.33%. MS[M+H] + 324.2, MS[M-H] - 322.2.

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Abstract

The invention relates to the field of medicinal chemistry, and in particular relates to 2-phenylaminopurine compounds, a preparation method for the compounds, a medicinal composition containing the compounds, and medical applications for the compounds, and in particular an application for the compounds as Polo-like kinase 1 inhibitors.

Description

technical field [0001] The present invention relates to the field of medicinal chemistry, in particular to 2-anilinopurine derivatives, their preparation methods, pharmaceutical compositions containing these compounds and their medical applications, especially as Polo-like kinase 1 (Polo-like kinase 1, Use of PLK1) inhibitors. Background technique [0002] In recent years, tumors have surpassed cardiovascular diseases and become the world's leading cause of death. The research on anti-tumor drugs has important academic and practical significance. [0003] Studies have found that almost all tumors are related to uncontrolled cell growth, blocked differentiation, and abnormal apoptosis caused by the disorder of cell cycle regulation mechanism. The frequency of tumor cell division is faster than that of normal cells, and various proteins that regulate microtubule polymerization, centrosome duplication, spindle formation, and cytokinesis are often overexpressed and their activi...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D473/32A61K31/52A61K31/5377A61P35/00A61P7/00
Inventor 卢帅张亮刘海春孙善亮陈亚东陆涛
Owner CHINA PHARM UNIV
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