Supercharge Your Innovation With Domain-Expert AI Agents!

Phosphine-containing macrocyclic compound, and preparation method and application thereof

A technology of macrocyclic compounds and compounds, applied in chemical instruments and methods, compounds of Group 5/15 elements of the periodic table, medical preparations containing active ingredients, etc., can solve problems such as treatment failure and drug resistance

Pending Publication Date: 2021-10-26
GUANGZHOU BIOTING PHARM TECH CO LTD
View PDF4 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, most patients fail treatment due to mutations in the ALK gene and drug resistance after treatment.

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
  • Phosphine-containing macrocyclic compound, and preparation method and application thereof
  • Phosphine-containing macrocyclic compound, and preparation method and application thereof
  • Phosphine-containing macrocyclic compound, and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0088]

[0089] 10-Dimethylphosphinyl-6-chloro-17-(4-(4-methylpiperazin-1-yl)-piperidin-1-yl)-19-methoxy-2,4,8 ,22-Azatetracyclo-[14.3.1.1 3,7 .1 9,13 ]22cyclo-1(20),3(22),4,6,9(21),10,12,16,18-nonene; MS (ESI) m / z 610.27 [M+H]+.

[0090]

[0091] Step 1: Cool concentrated nitric acid (25.9mmol) to 0°C, slowly add compound 1 (1g, 4.31mmol), continue to stir for 4h, pour the reaction solution into ice water, filter the solid, wash with water, and use di Phosphorus was dried and the crude product was recrystallized (0.45 g, 37%), LC / MS: 278.

[0092] Step 2: Dissolve methyltriphenylphosphine bromide (7.22mmol) in 10ml THF, cool down to -78°C, slowly add n-butyllithium (5.78mmol), and react at room temperature for 30min. The temperature of the reaction solution was lowered to -78°C, compound 2 (3.61 mmol) was dissolved in 4 ml of THF, the above reaction solution was slowly added dropwise, and the reaction was continued at room temperature. TLC monitoring. After the react...

Embodiment 2

[0102]

[0103] 19-methoxy-10-dimethylphosphinyl-6-chloro-17-(4-methylpiperazin-1-yl)-2,4,8,22-azatetracyclo-[14.3. 1.1 3,7 .1 9,13 ]22 cyclo-1(20),3(22),4,6,9(21),10,12,16,18-nonene.

[0104] The preparation of the compound of Example 2 refers to step 1 to step 10 in Example 1, wherein 1-methyl-4-(4-piperidinyl) piperazine in step 6 is replaced by 1-methylpiperazine of equimolar concentration . MS (ESI) m / z 527.20 [M+H]+.

Embodiment 3

[0106]

[0107] 10-Dimethylphosphinyl-6-chloro-17-(4-(4-methylpiperazin-1-yl)-piperidin-1-yl)-2,4,8,22-azatetra ring-[14.3.1.1 3,7 .1 9,13 ]22 cyclo-1(20),3(22),4,6,9(21),10,12,16,18-nonene.

[0108] The preparation of the compound of Example 3 refers to steps 1 to 10 in Example 1, wherein the 1-bromo-2-fluoro-4-methoxy-5-nitrobenzene in step 6 is composed of 2-bromo- 1-fluoro-4-nitrobenzene instead. MS (ESI) m / z 580.26 [M+H]+.

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 present invention relates to a phosphine-containing macrocyclic compound, and a pharmaceutically acceptable salt thereof, or a solvate thereof. The compound provided by the invention can effectively inhibit the activity of ALK kinase and related mutant kinase, and can effectively inhibit cancer cell proliferation.

Description

[0001] This application claims the priority of the Chinese patent application with the application number 202010554936.4 and titled "A Phosphine-Containing Macrocyclic Compound and Its Preparation and Application" filed with the China Patent Office on June 17, 2020, the entire contents of which are incorporated by reference incorporated in this application. technical field [0002] The invention relates to the field of cancer prevention and treatment, in particular to a phosphine-containing macrocyclic compound and its preparation method and application. Background technique [0003] Anaplastic lymphoma kinase (ALK) belongs to one of the insulin receptor superfamily of receptor tyrosine kinases. Normally, ALK plays an important role in the development and growth of the brain. The abnormality of ALK is closely related to the occurrence and development of tumors. ALK causes abnormal proliferation of cells and induces tumors through the mechanism of gene mutation, gene amplif...

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): C07F9/6561A61K31/675A61P35/00
CPCC07F9/6561A61P35/00
Inventor 徐伟吴曙光
Owner GUANGZHOU BIOTING PHARM TECH CO LTD
Features
  • R&D
  • Intellectual Property
  • Life Sciences
  • Materials
  • Tech Scout
Why Patsnap Eureka
  • Unparalleled Data Quality
  • Higher Quality Content
  • 60% Fewer Hallucinations
Social media
Patsnap Eureka Blog
Learn More

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2025 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com