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

N,N'-bis-substituted urea Raf kinase inhibitors and preparation method and application thereof

A C1-C6, general formula technology, applied in the preparation of urea derivatives, chemical instruments and methods, preparation of organic compounds, etc., can solve problems such as adverse reactions and limited treatment range

Active Publication Date: 2013-02-27
深圳澳美制药技术开发有限公司
View PDF0 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Many cytotoxic drugs have limited therapeutic range and are prone to treatment-related adverse effects

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
  • N,N'-bis-substituted urea Raf kinase inhibitors and preparation method and application thereof
  • N,N'-bis-substituted urea Raf kinase inhibitors and preparation method and application thereof
  • N,N'-bis-substituted urea Raf kinase inhibitors and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0087] 1H-Benzo[d]imidazole-2-carbonyl chloride (I-1)

[0088] Add 8.1 g (50 mmol) of 1H-benzo[d]imidazole-2-carboxylic acid and 40 mL of thionyl chloride into a 150 mL single-necked bottle, and heat to reflux for 4 hrs. The thionyl chloride was distilled off under reduced pressure to obtain 7.7 g of yellow solid (I-1) with a yield of 86.0%. The product did not need further purification and was directly used for the next reaction.

Embodiment 2

[0090] N-[2-(4-nitrophenyl)ethyl]-1H-benzo[d]imidazole-2-carboxamide (I-2)

[0091] Add 4-nitrophenethylamine 9.6g (58mmol), anhydrous chloroform 50mL and anhydrous triethylamine 5mL in 250mL three-necked bottle, slowly drop the chloroform suspension of 1-17.0g (38.7mmol) at room temperature ( 25 mL), heated to reflux for 4 hr after the addition, and TLC detected that the starting material disappeared (methanol:chloroform=1:30). Chloroform was distilled off, about 50 mL of water was added, stirred, allowed to stand, and suction filtered to obtain 9.94 g of yellow solid (I-2), with a yield of 83.1%. The product did not need further purification and was directly used for the next reaction. 1 H-NMR [300MHz, DMSO-d 6 ]: δ13.16(1H, s, benzimidazole-NH); 9.04(1H, t, CO-NH); 8.13(2H, dd, ArH); 7.69(1H, m, ArH); 7.56(1H, m, ArH); 7.53 (2H, dd, ArH); 7.28 (2H, m, ArH); 83.61 (2H, q, CH 2 ); δ3.05(2H, t, CH 2 ).

Embodiment 3

[0093] N-[2-(4-aminophenyl)ethyl]-1H-benzo[d]imidazole-2-carboxamide (I-4)

[0094] Add I-29g (29mmol), iron powder 6.5g (116mmol), NH 4 Cl 3.1g (58mmol) and 75% ethanol (100mL) were heated to reflux for 5hrs, and the starting material disappeared as detected by TLC (methanol:chloroform=1:30). Suction filtration while hot, and the filter cake was washed with a small amount of ethanol. Most of the solvent was evaporated under reduced pressure, extracted 3 times with ethyl acetate (20mL×3), the combined extracts were washed once with water and saturated sodium chloride (20mL×1), and the solvent was evaporated under reduced pressure to obtain a yellow oil. The crude product was subjected to column chromatography (developing solvent: methanol: chloroform = 1:30) to obtain I-45.74g with a yield of 70.6%. 1 H-NMR [300MHz, DMSO-d 6 ]: δ13.16 (1H, s, benzimidazole); 8.82 (1H, t, CO-NH); 7.69 (1H, m, ArH); 7.53 (1H, m, ArH); 7.28 (2H, m, ArH) ; 6.88 (2H, dd, ArH); 6.74 (2H, dd, ArH...

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 the field of pharmaceutical chemistry, in particular to N,N'-bis-substituted urea compounds, a preparation method thereof, a medicinal composition containing the compounds and medical application of the N,N'-bis-substituted urea compounds, particularly application of the N,N'-bis-substituted urea compounds used as a Raf kinase inhibitor.

Description

field of invention [0001] The present invention relates to the field of medicinal chemistry, in particular to a kind of N,N'-disubstituted urea compounds, their preparation method, pharmaceutical composition containing these compounds and their medical application, especially as the application of Raf kinase inhibitor . Background technique [0002] Tumor is a major disease that threatens human health. The treatment of tumor has been paid close attention to all over the world. Traditional chemotherapy drugs non-specifically block cell division and cause cell death. While killing tumor cells, they also destroy normal cells in the human body. Many cytotoxic drugs have limited therapeutic range and are prone to treatment-related adverse reactions. Targeting specific pathways can prevent tumor growth and reduce toxicity to normal cells. [0003] The Ras / Raf / MEK / ERK signal transduction pathway exists in most cells, and transduces extracellular stimulus signals to cells and th...

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): C07D235/24C07D209/42C07D207/34C07D471/04C07D233/90C07C275/40C07C273/18A61K31/437
Inventor 唐伟方陆涛颜彩虹林国武陈亚东张陆勇
Owner 深圳澳美制药技术开发有限公司
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