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
View PDF1 Cites 7 Cited by
  • 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

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • 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.

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

No PUM Login to view more

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

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
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
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap