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

Nitrogenous heterocyclic compound, preparation method, intermediates, composition and application

一种氮杂环化合物、杂环基的技术，应用在含氮杂环化合物领域，能够解决毒副作用多、ErbB2选择性低、安全性低等问题

Active Publication Date: 2017-09-08
SHANGAI PHARMA GRP CO LTD
View PDF5 Cites 20 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] The problem to be solved by the present invention is that existing compounds have defects such as low selectivity to ErbB2, many toxic and side effects, and low safety, and a nitrogen-containing heterocyclic compound, preparation method, intermediate, composition and application are provided.

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
  • Nitrogenous heterocyclic compound, preparation method, intermediates, composition and application
  • Nitrogenous heterocyclic compound, preparation method, intermediates, composition and application
  • Nitrogenous heterocyclic compound, preparation method, intermediates, composition and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 2

[0306]

[0307] N 4 -(4-([1,2,4]triazolo[1,5-c]pyrimidin-7-yloxy)-3-methylphenyl)-N 6 Synthesis of -(4,4-Dimethyl-4,5-dihydrooxazol-2-yl)quinazoline-4,6-diamine

[0308] Step A: Preparation of (E)-N'-(2-cyano-4-nitrophenyl)-N,N-dimethylformamidine: 2-amino-5-nitrobenzyl nitrile (11.5 g, 2.91mmol) was dissolved in N,N-dimethylformamide dimethyl acetal (40mL), heated to 100°C and stirred for 2 hours. After the reaction was completed, the solvent was directly evaporated to dryness under reduced pressure to obtain 15.1 g of light yellow solid, which was directly used in the next reaction.

[0309] Step B: Preparation of (E)-N'-(4-amino-2-cyanophenyl)-N,N-dimethylformamidine: (E)-N'-(2-cyano-4 -Nitrophenyl)-N,N-dimethylformamidine (1.0g, 4.58mmol) was dissolved in methanol:cyclohexene (5:1) mixed solvent (60mL), palladium carbon (10%, 100mg ), reacted under the protection of a hydrogen balloon, heated to 80 degrees and stirred for 18 hours. After the reaction was completed,...

Embodiment 3

[0316]

[0317] N 6 -(4,4-Dimethyl-4,5-dihydrooxazol-2-yl)-N 4 Synthesis of -(4-(imidazo[1,2-c]pyrimidin-7-yloxy)-3-methylphenyl)-4,6-diaminoquinazoline

[0318] Step A: Preparation of 4-chloro-6-(2-methyl-4-nitrophenoxy)pyrimidine: Dissolve 4,6-dichloropyrimidine (1.5 g, 10.07 mmol) in 30 mL of N.N-dimethyl Add 2-methyl-4-nitrophenol (1.5g, 9.81mmol) and solid potassium carbonate (1.5g, 10.87mmol) to formamide, heat to 80°C and stir overnight. After the reaction was completed, 40 mL of ethyl acetate was added, stirred, filtered, and the filtrate was evaporated to dryness under reduced pressure. The residue was separated by column chromatography to obtain 2.3 g of a light yellow solid, with a yield of 88.46%.

[0319] Step B: Preparation of 6-(2-methyl-4-nitrophenoxy)-4-aminopyrimidine: 4-chloro-6-(2-methyl-4-nitrophenoxy)pyrimidine ( 1.2g, 4.51mmol) was dissolved in 20mL of ethanol and 60mL of ammonia solution, sealed tube and stirred at 120°C for 18 hours. After the r...

Embodiment 4

[0325]

[0326] N 4 -(4-([1,2,4]-triazolo[4,3-c]pyrimidin-7-yloxy)-3-toluene)-N 6 Synthesis of -(4,4-Dimethyl-4,5-dihydrooxazol-2-yl)-4,6-diaminoquinazoline

[0327] Step A: Preparation of 2-chloro-6-hydrazinopyrimidine: 2,6-dichloropyrimidine (25g, 167.81mmol) was dissolved in 350mL isopropanol, and hydrazine hydrate (29.5g, 503.44 mmol, 85%), exothermic during the dropwise addition and a white solid precipitated, and stirred at room temperature for 1 hour after the addition. The solvent was removed under reduced pressure, the residue was stirred with water (50 mL) for 30 minutes, filtered, the filter cake was washed with water, and dried to obtain 22.4 g of a white solid with a yield of 92.3%.

[0328] Step B: Preparation of 7-chloro-[1,2,4]triazolo[4,3-c]pyrimidine: 2-chloro-6-hydrazinopyrimidine (21 g, 145.27 mmol) was dispersed in 210 mL of trimethylorthoformate The ester was stirred overnight at 60°C, and the reaction liquid became clear. Add p-toluenesulfonic aci...

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 a nitrogenous heterocyclic compound, a preparation method, intermediates, a composition and application. The nitrogenous heterocyclic compound is as shown in the formula I, has high inhibitory activity to ErbB2 tyrosine kinase, has relatively good inhibitory activity to ErbB2 high-expression human breast cancer cells BT-474, human gastric carcinoma cells NCI-N87 and the like, meanwhile, has relatively weak inhibitory activity to EGFR kinase, is a small-molecule inhibitor with good selectivity to ErbB2 target spots, therefore, is high in safety and can effectively enlarge the safety window in the medicine administration process.

Description

technical field [0001] The invention relates to a nitrogen-containing heterocyclic compound, a preparation method, an intermediate, a composition and an application. Background technique [0002] The epidermal growth factor receptor (EGFR, also known as ErbB or HER) family includes four receptor tyrosine kinases, namely EGFR (ErbB1 or HER1), ErbB2 (HER2), ErbB3 (HER3) and ErbB4 (HER4). Several investigators have demonstrated the role of EGFR and ErbB2 in cancer progression, and squamous cell carcinomas of the head, neck and lung also express high levels of EGFR. Overexpression of ErbB2 occurs in 30% of all breast cancers and is also associated with other human cancers such as colon, ovary, bladder, stomach, esophagus, lung, uterus and prostate cancers. ErbB2 overexpression is also associated with poor prognosis in other cancers, including metastasis and early recurrence. [0003] The epidermal growth factor receptor family has become an active field of anticancer research,...

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): C07D487/04C07D519/00A61K31/519A61K31/541A61K31/5377A61P35/00
CPCC07D487/04A61K31/5377A61K31/519A61P35/00A61K31/5355A61K31/541Y02P20/55
Inventor 夏广新李迪左洪剑伍广生段灵峻张晶毛煜刘彦君
Owner SHANGAI PHARMA GRP 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