Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Novel CDK2 inhibitor and application thereof in resisting of breast cancer

A compound and pharmaceutical technology, applied in the field of anti-tumor pharmacy, can solve the problems of high toxicity and side effects, drug resistance, etc., and achieve the effect of inhibiting growth and obvious inhibition

Active Publication Date: 2018-05-04
SICHUAN UNIV
View PDF5 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, problems such as high toxicity and side effects and drug resistance are still the main obstacles encountered in clinical tumor drug treatment.

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
  • Novel CDK2 inhibitor and application thereof in resisting of breast cancer
  • Novel CDK2 inhibitor and application thereof in resisting of breast cancer
  • Novel CDK2 inhibitor and application thereof in resisting of breast cancer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0069] Example 1 Synthesis of Compounds 1-24.

[0070] Compounds 1-24 were synthesized using the following reaction formula:

[0071]

[0072]

[0073] (a) DIEA, ethanol, at room temperature or 78°C; or DIEA, tert-butanol, at 75°C;

[0074] (b) DIEA, n-butanol, 120°C;

[0075] (c) trifluoroacetic acid, dichloromethane, room temperature;

[0076] (d) Triethylamine, dichloromethane, room temperature.

[0077] 1. The synthetic method of intermediate C1-4.

[0078] The synthesis method of intermediate C1 is to dissolve the raw material 2,4-dichloropyrimidine (1 mmol) in 100 mL of ethanol, add N,N-diisopropylethylamine (DIEA, 1.5 eq) at room temperature, and then add p-fluoroaniline ( 1.1 eq). Stir at room temperature for 8 hours, terminate the reaction, and filter with suction to obtain a solid as intermediate C1.

[0079] The synthesis method of intermediate C2 is to dissolve the raw material 2,4-dichloropyrimidine (1 mmol) in 100 mL of ethanol, add N,N-diisopropyleth...

experiment example 2

[0133] Experimental example 2 Compound CDK2 enzyme activity inhibitory activity.

[0134] Enzyme inhibition assay in 20 ml of 50 mM Tris-HCl containing 10 mM ATP, 0.2 mCi γ 32 P-ATP, 10mM MgCl 2 , 5 mM DTT, 4 mg histone H1 as substrate. After adding the inhibitor, react for 10 minutes and immediately quench with 10 ml of 30% phosphoric acid. Then transferred to P81 paper and washed 5 times with 10 mM Tris-HCl (pH=8) containing 0.1 M NaCl solution. Then detect its radioactivity.

[0135] Compound CDK2 Enzyme Activity Screening

[0136]

[0137]

[0138]

[0139]

[0140] The above experimental results show that these compounds have strong to moderate inhibitory activity on CDK2, among which compound 11 shows the strongest inhibitory activity, IC 50 =45.8 nM.

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 a CDK2 inhibitor and application thereof, belonging to the technical field of anti-tumor pharmacy. The invention provides a compound as the CDK2 inhibitor. The compound contains a compound represented by a formula (shown in the description) or pharmaceutically acceptable salt of the compound. The compound or the pharmaceutically acceptable salt of the compound can be takenas the CDK2 inhibitor, has certain anti-tumor activity and is capable of effectively inhibiting the growth of cancer cells. The compound is capable of obviously inhabiting multiple tumor cells, particularly breast cancer cells.

Description

technical field [0001] The invention relates to a CDK2 inhibitor and application thereof, belonging to the technical field of antitumor pharmacy. Background technique [0002] Cancer is one of the main causes of death faced by human beings, and it seriously threatens human life and health. According to the statistics of the World Health Organization (WHO), there are about 11 million new cancer patients worldwide each year, and about 7 million people die of cancer, accounting for about a quarter of the total number of deaths. At present, there are 3.56 million new cancer cases in my country every year, and the incidence rate is generally on the rise; the mortality rate of existing cancer patients exceeds 30%, which has become the second largest factor in the death of Chinese residents. Drug therapy has become an effective and widely used treatment method for malignant tumors. Although Gilman of Yale University first proved that nitrogen mustard hydrochloride had a therapeut...

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): C07D401/04A61K31/506A61P35/00
CPCC07D401/04
Inventor 欧阳亮刘博符雷蕾张岚王贯
Owner SICHUAN UNIV
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com