Eureka AIR delivers breakthrough ideas for toughest innovation challenges, trusted by R&D personnel around the world.

Hydrazone-containing pyrimidine derivatives and use thereof

A technology of derivatives and compounds, applied in the field of hydrazone-containing pyrimidine derivatives and their uses, can solve problems such as ROS1 protein dysregulation

Active Publication Date: 2017-09-12
SHENYANG PHARMA UNIVERSITY
View PDF2 Cites 6 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Fusion, overexpression and mutation of ROS1 gene can lead to dysregulation of ROS1 protein

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
  • Hydrazone-containing pyrimidine derivatives and use thereof
  • Hydrazone-containing pyrimidine derivatives and use thereof
  • Hydrazone-containing pyrimidine derivatives and use thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0115] Step A Isopropyl(2-nitrophenyl)sulfide (Ⅱ)

[0116] Add 509.1g (3.61mol) of o-fluoronitrobenzene and 698.0g (5.06mol) of anhydrous potassium carbonate to 2500mL of dry N,N-dimethylformamide (DMF), slowly drop into 301.8g (3.97mol ) isopropyl mercaptan, after dropping, the temperature was raised to 110° C. for 10 h. After cooling to room temperature, the reaction solution was poured into a large amount of water, extracted with ethyl acetate, dried over anhydrous sodium sulfate, and evaporated to dryness to obtain 604.6 g of a yellow liquid with a yield of 85.0%.

[0117] Step B 1-Isopropylsulfonyl-2-nitrobenzene (Ⅲ)

[0118] Add 197.1g (1.00mol) of isopropyl (2-nitrophenyl) sulfide to 1500mL of glacial acetic acid, slowly drop into 583.0g (6.00mol) of 35% hydrogen peroxide, raise the temperature to 80°C, and react for 9h. After cooling to room temperature, the reaction solution was poured into a large amount of water, stirred at room temperature for 30 min, filtered wi...

Embodiment 2

[0129] Example 2 (E)-5-chloro-N-(2-(isopropylsulfonyl)phenyl)-2-(2-(pyridin-4-ylmethylene)hydrazino)pyrimidin-4-amine

[0130] ESI-MS [M+H] (m / z): 431.1; 1 H NMR(400MHz,DMSO)δ11.69(s,1H),9.80(s,1H),9.21(s,1H),8.36(s,1H),8.10(s,1H),7.88(t,J= 7.8Hz, 2H), 7.64(d, J=5.8Hz, 2H), 7.40(t, J=7.6Hz, 1H), 3.58–3.45(m, 1H), 1.20(d, J=6.8Hz, 6H) .

Embodiment 3

[0131] Example 3 (E)-5-chloro-N-(2-(isopropylsulfonyl)phenyl)-2-(2-(pyridin-3-ylmethylene)hydrazino)pyrimidin-4-amine

[0132] ESI-MS [M+H] (m / z): 431.1;

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 hydrazone-containing pyrimidine derivatives represented by general formula I, and optical isomers, pharmaceutically acceptable salts, solvates or prodrugs thereof, a preparation method of above compounds, and a medicinal composition adopting the compounds represented by the general formula I as an active component. Substituent groups R1, R2, R3, Ar and X in the general formula I are as defined in the description. The invention also relates to a strong ALK and ROS1 kinase inhibition effect of the compounds of the general formula I, and an application of the compounds, and the optical isomers and pharmaceutically acceptable salts thereof in the preparation of medicines for treating and / or preventing ALK and ROS1 abnormal expression induced disease, and especially a use in the preparation of medicines for treating and / or preventing cancers.

Description

technical field [0001] The present invention relates to hydrazone-containing pyrimidine derivatives and optical isomers, pharmaceutically acceptable salts, solvates or prodrugs, their preparation methods and pharmaceutical compositions containing the compounds. The present invention also relates to the strong ALK and ROS1 kinase inhibitory effect of the compound, and also relates to the preparation of such compounds and their optical isomers and pharmaceutically acceptable salts for the treatment and / or prevention of ALK and ROS1 abnormalities The application of the drug expressing the caused disease, especially the application in the preparation of the drug for the treatment and / or prevention of cancer. Background technique [0002] The research on kinase target drugs has become an important direction in the research and development of anticancer drugs. Among the currently discovered kinase target drugs, protein kinases are known to be the most studied class. Due to mutat...

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): C07D239/48C07D401/12C07D409/12C07D405/12A61K31/505A61K31/506A61P35/00
CPCA61K9/0014A61K9/02A61K9/06A61K9/08A61K9/2063A61K9/7007A61K47/06A61K47/10A61K47/32A61K47/42C07D239/48C07D401/12C07D405/12C07D409/12
Inventor 宫平翟鑫刘亚婧赵燕芳王昱
Owner SHENYANG PHARMA UNIVERSITY
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
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