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

Diaminodihydrotriazine derivative, its salt, preparation method, composition and application

A technology of diaminodihydrotriazine and derivatives, which is used in drug combinations, active ingredients of heterocyclic compounds, bone diseases, etc., can solve the problem of difficult to find out the effect of activity, and has not been studied related to triazine spiroheterocyclic compounds. Properties, no reports on the structure-activity relationship of diaminodihydrotriazine spiroheterocyclic compounds, etc.

Active Publication Date: 2016-02-10
SHANGHAI INST OF PHARMA IND CO LTD +1
View PDF4 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] Ma Xiang and others have synthesized a series of diaminodihydrotriazine compounds with spiro ring structure (XiangMa, ReneeSer-PengWoon, AntiproliferativeActivity AgainstMCF-7BreastCancerCellsbyDiamino-TriazaspirodieneAntifolates, Chem.Biol.DrugDes.2009;74:322-326), and Corresponding biological activity tests were done respectively, which involved Compound 1, Compound 2, and Compound 3 as shown below, but the relevant properties of triazine spiroheterocyclic compounds were not studied in the above reports, nor were there any studies on the two compounds in the prior art. Research reports on the structure-activity relationship of aminodihydrotriazine spiroheterocyclic compounds, so the structural modification of this type of compound is always subject to certain restrictions, and it is difficult to find out the impact of their structure on the activity. Therefore, for this type of compound Research still needs to be further deepened

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
  • Diaminodihydrotriazine derivative, its salt, preparation method, composition and application
  • Diaminodihydrotriazine derivative, its salt, preparation method, composition and application
  • Diaminodihydrotriazine derivative, its salt, preparation method, composition and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0175] 1-Bromo-3-phenoxypropane

[0176] Phenol (4.7g, 0.05mol), 1,3-dibromopropane (50g, 0.25mol), and potassium carbonate (10g, 0.075mol) were mixed in 100ml of acetonitrile, and reacted at 80°C for 9 hours. When the phenol is consumed as monitored by TLC, stop the reaction, place it at room temperature, remove the solid by suction filtration, concentrate the filtrate under reduced pressure, add 100ml of chloroform, wash the chloroform layer twice with 0.2N aqueous sodium hydroxide solution (100ml*2), wash with anhydrous magnesium sulfate to dry. Distilled under reduced pressure, under the pressure of 0.48mbar, the fraction at 76-78°C was taken to obtain 6.7g of colorless oil, with a yield of 62.2%. References for specific methods (Hideki Kubota, Toshihiro Watanabe. Synthesis and pharmacological evaluation of N-acyl-1,2,3,4-tetrahydroisoquinoline derivatives as novel specific bradycardicagents. Bioorganic & Medicinal Chemistry, 2004, 12:871-882).

[0177] Compounds of gene...

Embodiment 2

[0179] 1-bromo-3-(2’,4’-dichlorophenoxy)propane

[0180] 2,4-dichlorophenol (8.2g, 0.05mol), 1,3-dibromopropane (50g, 0.25mol), and potassium carbonate (10g, 0.075mol) were mixed in 100ml of acetonitrile and reacted at 80°C for 8 hours. When the phenol is consumed as monitored by TLC, stop the reaction, place it at room temperature, remove the solid by suction filtration, concentrate the filtrate under reduced pressure, add 100ml of chloroform, wash the chloroform layer twice with 0.2N aqueous sodium hydroxide solution (100ml*2), wash with anhydrous magnesium sulfate to dry. Distilled under reduced pressure, under 0.3mbar pressure, the fraction at 106-108°C was taken to obtain 8.5g of colorless oily substance, with a yield of 60.5%.

Embodiment 3

[0182] 1-Bromo-3-(4’-methoxyphenoxy)propane

[0183] 4-Methoxyphenol (6.2g, 0.05mol), 1,3-dibromopropane (50g, 0.25mol), and potassium carbonate (10g, 0.075mol) were mixed in 100ml of acetonitrile, and reacted at 80°C for 9 hours. When the phenol is consumed as monitored by TLC, stop the reaction, place it at room temperature, remove the solid by suction filtration, concentrate the filtrate under reduced pressure, add 100ml of chloroform, wash the chloroform layer twice with 0.2N aqueous sodium hydroxide solution (100ml*2), wash with anhydrous magnesium sulfate to dry. Distilled under reduced pressure, under 0.5mbar pressure, the fraction at 98-102°C was taken to obtain 8.1g of colorless oily substance, with a yield of 66.1%.

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 discloses derivatives and salts of damino dihydrotriazine, and a preparation method, a composition and application thereof. According to the invention, the preparation method of the damino dihydrotriazine derivative and the damino dihydrotriazine salt can be realized by adopting a method I or a method II, wherein the method I includes the step of obtaining a general formula I compound prepared through the reaction between a general formula IV compound and a general formula V compound, while the method II includes the step of mixing a general formula VIII compound with a general formula II compound under an acidic condition, and obtaining the compound shown in the general formula I through a cyclization reaction of the mixture. The invention also provides application of derivatives and salts of the damino dihydrotriazine in preparation of human dihydrofolate reductase inhibitors, preventing and curing drugs for tumor or bacterial infection diseases. The invention further provides a drug composition, which comprises an effective amount of the derivatives and / or salts of the damino dihydrotriazine, as well as pharmaceutically acceptable carriers. According to the invention, spiro heterocyclic ring derivatives of the damino dihydrotriazine have an excellent inhibitory activity on human dihydrofolate reductase, tumor cells and bacteria.

Description

technical field [0001] The invention belongs to the technical field of pharmaceutical chemical synthesis, and specifically relates to a diaminodihydrotriazine derivative with a spiro ring structure, a salt thereof, a preparation method, a composition containing the same and an application. Background technique [0002] Dihydrofolate reductase (DHFR) in the biometabolism of folic acid is an important drug target. Dihydrofolate reductase is a key enzyme in the biological metabolism of folic acid. Its main function is to catalyze the reduction of dihydrofolate to tetrahydrofolate in organisms, and tetrahydrofolate is an essential coenzyme in the process of DNA synthesis. The structure of DHFR inhibitors is similar to the substrate of dihydrofolate reductase, which can competitively combine with DHFR, hinder the combination of DHFR and normal substrates, inhibit its catalytic reduction activity, and make it difficult to convert dihydrofolate into tetrahydrofolate. Interfering w...

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): C07D491/107C07D495/10A61K31/53A61P35/00A61P31/04A61P35/02A61P37/02A61P19/02A61P19/04
CPCC07D491/107C07D495/10
Inventor 周晓天林快乐周伟澄
Owner SHANGHAI INST OF PHARMA IND 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