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

Pteridinone derivatives as BLK and FLT3 inhibitors and applications thereof

A compound, pyridyl technology, applied in the direction of anti-inflammatory agents, drug combinations, non-central analgesics, etc., can solve problems such as unsatisfactory clinical effects

Inactive Publication Date: 2014-06-04
EAST CHINA UNIV OF SCI & TECH
View PDF0 Cites 11 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

So far, no FLT3 inhibitor has been approved for clinical use, and the clinical effects of many FLT3 inhibitors in clinical trials are still not ideal

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
  • Pteridinone derivatives as BLK and FLT3 inhibitors and applications thereof
  • Pteridinone derivatives as BLK and FLT3 inhibitors and applications thereof
  • Pteridinone derivatives as BLK and FLT3 inhibitors and applications thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0101] The concrete synthetic method of above-mentioned steps a-f is as follows:

[0102] Synthesis of tert-butyl (4-(2-chloro-5-nitropyrimidine-4-amino)phenyl)carbamate (step a)

[0103]

[0104] Weigh 2,4-chloro-5-nitropyrimidine (95mg, 0.49mmol) into a 10mL round bottom flask, add 3mL 1,4-dioxane, stir at room temperature, and take another (4-aminophenyl ) tert-butyl carbamate (100mg, 0.48mmol), N,N-isopropylethylamine (69mg, 0.53mmol) were dissolved in 2mL 1,4-dioxane, and added dropwise to the above reaction solution, dropwise After the addition was complete, the mixture was stirred at room temperature for 0.5 hour, followed by TLC until the starting material was completely converted. The solvent was removed by rotary evaporation, and the crude product was separated by silica gel column chromatography (petroleum ether / ethyl acetate=10:1, v / v) to obtain (4-(2-chloro-5-nitropyrimidine-4-amino)phenyl ) tert-butyl carbamate orange solid 144mg, yield 82%. 1 H NMR (400MHz, ...

Embodiment 2

[0212] Biological Activity Test Section

[0213] The experiment of the in vitro inhibitory effect of the compounds provided by the invention on the kinase activity of BLK and FLT3 was carried out as follows, wherein BLK and FLT3 were purchased from BPS, and staurosporine was used as a control compound.

[0214] Prepare 1x Kinase Substrate Buffer and Stop Buffer. 1x Kinase Substrate Buffer: 50mM HEPES, pH 7.5, 0.0015% Brij-35, 10mM Magnesium Chloride, 2mM DTT; Stop Buffer: 100mM HEPES, pH 7.5, 0.0015% Brij-35, 0.2% Coating Reagent#3, 50mM EDTA. Prepare compound solutions. Dissolve the compound in 100% DMSO, prepare a solution of 50 times the final maximum inhibitory concentration, and transfer 100 μL of the above solution to a 96-well plate; dilute the above compound solution to the final required concentration in sequence; two in the same 96-well plate Add 100 μL of 100% DMSO to the blank well as the no-compound and no-kinase control, this well plate is used as the original ...

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 pteridinone derivatives as BLK and FLT3 inhibitors and applications thereof. Particularly, the invention relates to a compound shown in the following formula I, a pharmaceutical composition containing the compound shown in the following formula I, and use of the compound in preparation of a drug for treating BLK and FLT3-mediated diseases or inhibiting BLK and FLT3.

Description

technical field [0001] The present invention relates to the synthesis of pteridinone compounds and their applications in the fields of medicinal chemistry and pharmacotherapeutics, specifically, the application of pteridinone compounds with different substituents in the preparation of drugs for tumors and immune diseases. application. Background technique [0002] Protein tyrosine kinase (protein tyrosine kinase) is a class of proteins that catalyze the transfer of γ-phosphate on ATP to specific amino acid residues in proteins. It plays a very important role in intracellular signal transduction pathways and regulates cell growth, A series of physiological processes such as differentiation and death. It has been shown that more than 50% of proto-oncogenes and their products have protein tyrosine kinase activity, and their abnormal expression will lead to the disorder of cell life cycle, and then lead to the occurrence of tumors. In addition, abnormal expression of tyrosine ...

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
IPC IPC(8): C07D487/04A61K31/519A61K31/5377A61P35/00A61P37/02A61P35/02A61P19/02A61P1/00A61P3/10A61P21/04A61P29/00A61P25/00A61P1/16A61P37/06A61P37/08A61P27/02A61P11/02A61P17/00
CPCC07D475/00
Inventor 李洪林徐玉芳赵振江刘晓峰周伟白芳薛梦竹张磊张友利
Owner EAST CHINA UNIV OF SCI & TECH
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