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

Triazine Derivatives Anaplastic Lymphoma Kinase Inhibitors

An inhibitor, lymphoma technology, applied in the field of triazine derivative anaplastic lymphoma kinase inhibitors, which can solve problems such as easy generation of drug resistance

Active Publication Date: 2019-07-16
SHANDONG XUANZHU PHARMA TECH CO LTD +1
View PDF6 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, Pfizer's Crizotinib has been successfully marketed, but a large number of clinical trials have proved that the first-generation ALK inhibitor Crizotinib is prone to drug resistance. Therefore, designing and screening patients who are resistant to Crizotinib also has good curative effect A second-generation ALK inhibitor with significant clinical significance

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
  • Triazine Derivatives Anaplastic Lymphoma Kinase Inhibitors
  • Triazine Derivatives Anaplastic Lymphoma Kinase Inhibitors
  • Triazine Derivatives Anaplastic Lymphoma Kinase Inhibitors

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0088] The present invention also provides the preparation method of above-mentioned compound, but not limited to following method, and reaction equation is as follows:

[0089]

[0090] Reaction steps:

[0091] The preparation of step 1 intermediate 1

[0092] Intermediate 1 can be purchased or prepared by appropriate methods.

[0093] Step 2 Preparation of Intermediate 2

[0094] Intermediate 1 is dissolved in a solvent (such as N,N-dimethylformamide), added N-bromosuccinimide, heated (such as 50-70°C) overnight, the reaction is complete, quenched with water, organic solvent (eg ethyl acetate) extraction, concentration and purification (eg silica gel column chromatography) to obtain intermediate 2.

[0095] Step 3 Preparation of Intermediate 3

[0096] Dissolve intermediate 2 in a suitable solvent (such as ethanol), add an organic solvent (such as acetic acid), heat (such as 70°C), add iron powder, heat up (such as 80°C), react (such as 2-4 hours), and react Complete...

experiment example 1

[0125] Experimental Example 1 The in vitro enzymatic activity test of the compound of the present invention

[0126] Test product: trifluoroacetate salt of compound 1 of the present invention, its chemical name and preparation method are shown in the preparation example of trifluoroacetate salt of compound 1.

[0127] The meanings represented by the abbreviations of the following experiments are as follows:

[0128] DMSO: dimethyl sulfoxide

[0129] DTT: Dithiothreitol

[0130] SEB: Enzyme Catalyst Buffer

[0131] ATP: adenosine triphosphate

[0132] ALK: Anaplastic Lymphoma Kinase

[0133] SA-XL665: Streptavidin-labeled donor

[0134] 2.5×, 5×, 10× “×” among them: times

[0135] experimental method:

[0136] ALK kinase buffer preparation:

[0137] Take an appropriate amount of MgCl with a mother liquor concentration of 1000mM 2 , 2500nM SEB, 100mM DTT, and 5×enzyme buffer were added to ultrapure water so that the final concentrations were: 5mM, 25nM, 1mM, and 1×enzy...

specific Embodiment approach

[0155] The above-mentioned content of the present invention will be further described in detail through specific implementation in the form of examples below. However, it should not be construed that the scope of the above-mentioned subject matter of the present invention is limited to the following examples. All technologies realized based on the above contents of the present invention belong to the scope of the present invention.

[0156] The definitions represented by the following abbreviations are as follows:

[0157] DMF: N,N-Dimethylformamide

[0158] Pd(dppf)Cl 2 : [1,1'-bis(diphenylphosphino)ferrocene]palladium dichloride

[0159] DIPEA: Diisopropylethylamine

[0160] TFA: Trifluoroacetic acid

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 belongs to the technical field of medicines, and particularly relates to a triazine derivative anaplastic lymphoma kinase inhibitor shown in a general formula (I), pharmaceutically acceptable salt, ester, solvate or stereoisomer of the inhibitor. R1, R2, R3, R4, R6, R7 and A rings are defined in the description. The invention further relates to a preparation method of compounds, a medicinal preparation containing the compounds, a medicine combination containing the compounds and an application of the compounds, the pharmaceutically acceptable salt, ester, solvate or stereoisomer to preparation of a medicine for treating and / or preventing anaplastic lymphoma kinase-mediated cancer-related diseases.

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to triazine derivatives anaplastic lymphoma kinase inhibitors, pharmaceutically acceptable salts, esters, solvates or stereoisomers thereof, and methods for preparing these compounds, which contain these compounds Pharmaceutical preparations and pharmaceutical compositions, and the compound, its pharmaceutically acceptable salt, ester, solvate or stereoisomer thereof in the preparation of treatment and / or prevention of cancer-related diseases mediated by anaplastic lymphoma kinase application in medicine. Background technique [0002] Anaplastic lymphoma kinase (ALK) is a member of the receptor tyrosine kinase family, which can recruit downstream proteins through autophosphorylation, and then express specific genes to regulate cell metabolism and growth. Anaplastic lymphoma kinase was first discovered in anaplastic large cell lymphoma (ALCL), and later found to be high...

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 Patents(China)
IPC IPC(8): C07D405/14A61K31/53A61P35/00
CPCC07D405/14
Inventor 吴永谦
Owner SHANDONG XUANZHU PHARMA TECH CO LTD
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