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

Macrocyclic derivatives for treating tumor

A macrocyclic derivative, tumor technology, used in the field of compounds for the prevention and treatment of protein kinase-related diseases, pharmaceutical use of diseases, and compounds that regulate the activity of anaplastic lymphoma kinase, which can solve the incidence of adverse reactions in the digestive tract between QT issues such as extension

Active Publication Date: 2017-06-20
HANGZHOU LEISUO PHARMA
View PDF7 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Despite the remarkable efficacy of the drug, due to the characteristics of tumor heterogeneity and the adaptation of tumor cells to environmental pressure, more and more research reports have shown that tumor drug resistance and continued disease progression are almost the inevitable fate of such patients; in addition, now There are serious adverse reactions of drugs, such as high incidence of gastrointestinal adverse reactions, liver toxicity and QT interval prolongation, which also limit the application of this type of drugs

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
  • Macrocyclic derivatives for treating tumor
  • Macrocyclic derivatives for treating tumor
  • Macrocyclic derivatives for treating tumor

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0100] Embodiment 1, the preparation of [number is REX-MA-2]

[0101] The synthetic route is as follows:

[0102]

[0103] Synthesis Scheme 1: Synthesis of Intermediates 1-3

[0104] Step 1: Preparation of compound 1-2

[0105] Dissolve compound 1-1 (20.0g, 328.0mmol) in 2.0L of a mixed solvent of 1,4-dioxane and water (1,4-dioxane: water = 10:1), add hydrogen Add sodium (20.0g, 328.0mmol) dropwise in an ice-water bath and di-tert-butyl carbonate (77.0g, 354.0mmol), stir the reaction system at 0°C for 2 hours, add 2.0L saturated sodium bisulfate to the system after the reaction The solution was extracted with ethyl acetate, washed with saturated brine, dried over anhydrous sodium sulfate, concentrated and purified with a silica gel column to obtain compound 1-2 (45.4 g, 86.0%).

[0106] MS m / z [ESI]: 162.1 [M+1].

[0107] Step 2: Preparation of compound 1-3

[0108] Compound 1-2 (24.6g, 152.7mmol) was dissolved in 1.5L of dichloromethane, and triethylamine (42.7ml, 305...

Embodiment 2

[0164] Embodiment 2, the preparation of [number is REX-MA-5]

[0165] The synthetic route is as follows:

[0166]

[0167] Synthesis Scheme 1: Synthesis of Compound REX-MA-5

[0168] Step 1: Preparation of compound REX-MA-5

[0169] Referring to the preparation method of Example 1, the compound REX-MA-2 was first prepared, and then the compound REX-MA-2 (100.0mg, 0.16mmol) was dissolved in 2.0ml of dry tetrahydrofuran solution, and 1M borane tetrahydrofuran solution (1.60ml , 1.60mmol), the reaction system was stirred at 50°C for 18 hours, after the reaction was completed, anhydrous methanol was added to the system to quench, and after quenching, it was directly concentrated, and the concentrated solution was transferred to a sealed tube, and 2.0ml of anhydrous methanol was added to the Stir at 100°C for 6 hours, concentrate after the reaction, and purify with a silica gel column to obtain compound REX-MA-5 (63.6 mg, 66.0%).

[0170] MS m / z [ESI]: 603.3 [M+1].

[0171] 1...

Embodiment 3

[0172] Example 3, the preparation of [No. REX-MA-21]

[0173] The synthetic route is as follows:

[0174]

[0175]

[0176] Synthesis Scheme 1: Synthesis of Intermediates 1-3

[0177] Step 1: Preparation of compound 1-2

[0178] Compound 1-1 (24.6g, 328.0mmol) was dissolved in 2.0L of a mixed solvent of 1,4-dioxane and water (1,4-dioxane: water = 10:1), and the Add sodium (20.0g, 328.0mmol) dropwise in an ice-water bath and di-tert-butyl carbonate (77.0g, 354.0mmol), stir the reaction system at 0°C for 2 hours, add 2.0L saturated sodium bisulfate to the system after the reaction The solution was extracted with ethyl acetate, washed with saturated brine, dried over anhydrous sodium sulfate, concentrated and purified by silica gel column to obtain compound 1-2 (50.5 g, 88.0%).

[0179] MS m / z [ESI]: 176.1 [M+1].

[0180] Step 2: Preparation of compound 1-3

[0181] Compound 1-2 (26.7g, 152.7mmol) was dissolved in 1.5L of dichloromethane, and triethylamine (42.7ml, 305...

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 discloses compounds which are capable of regulating the protein kinase activity and are used for treatment or prevention of protein kinase related diseases. Specifically, the invention relates to macrocyclic derivatives for treating tumor, belongs to compounds for regulation of the activity of anaplastic lymphoma kinase (ALK), and provides a preparation method for the compounds, and a pharmaceutical use of the compounds for treatment or prevention of ALK related diseases.

Description

technical field [0001] The present invention relates to compounds that regulate protein kinase activity and are used for preventing and treating diseases related to protein kinase. Specifically, the present invention relates to a macrocyclic derivative used for the treatment of tumors, which belongs to the compound that regulates the activity of anaplastic lymphoma kinase (ALK), and provides a preparation method of this type of compound, and the use of this type of compound for preventing or pharmaceutical use in the treatment of diseases associated with ALK. Background technique [0002] Malignant tumor is a common and frequently-occurring disease that seriously threatens human health. It is characterized by abnormal proliferation of cells or mutant cells. The proliferation, apoptosis, and metastasis of tumor cells are closely related to the abnormality of a certain link in a series of signal transduction pathways inside and outside the cells. In these signaling pathways,...

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): C07D487/18C07D513/18C07D498/18A61P35/00
CPCC07D487/18C07D498/18C07D513/18
Inventor 王永辉朱研周娟高羽军王栋沈锡明吴耀东李春启
Owner HANGZHOU LEISUO PHARMA
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