Supercharge Your Innovation With Domain-Expert AI Agents!

2-(4-Morpholino)-4,6-disubstituted pyrimidine/s-triazine compounds, salts thereof, and application of compounds or salts

A disubstituted, morpholino-based technology, applied to 2--4,6-disubstituted pyrimidine or s-triazine compounds and their pharmaceutically acceptable salts and application fields, can solve problems such as poor clinical effects, and achieve anti-inflammatory properties. Good tumor activity

Inactive Publication Date: 2018-02-02
XI AN JIAOTONG UNIV
View PDF2 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The vast majority of kinase inhibitors reported in the literature are single-target or single-pathway kinase inhibitors, and the clinical effect is not good

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
  • 2-(4-Morpholino)-4,6-disubstituted pyrimidine/s-triazine compounds, salts thereof, and application of compounds or salts
  • 2-(4-Morpholino)-4,6-disubstituted pyrimidine/s-triazine compounds, salts thereof, and application of compounds or salts
  • 2-(4-Morpholino)-4,6-disubstituted pyrimidine/s-triazine compounds, salts thereof, and application of compounds or salts

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0033] The 2-(4-morpholinyl)-4-(N-alkyl-N-(1-benzoyl-4-piperidinyl) amino)-6-(pyridyl or pyrimidinyl) pyrimidine or The synthetic method of s-triazine compound comprises following three-step reaction:

[0034] Step 1: In the presence of alkaline reagents, 2,4,6-trichloropyrimidine or 2,4,6-trichloro-1,3,5-triazine and 4-substituted amino-1-benzoylpiperidine The intermediate M is obtained through a nucleophilic substitution reaction in an organic solvent;

[0035] Step 2: 2,6-dichloro-4-(N-alkyl-N-(1-benzoyl-4-piperidinyl)amino)-1,3,5-triazine or 2,6-di Chloro-4-(N-alkyl-N-(1-benzoyl-4-piperidinyl)amino)pyrimidine reacts with morpholine in an organic solvent to obtain intermediate N;

[0036] Step 3: Under the catalysis of the palladium complex, the intermediate N and the substituted 3-pyrimidinyl borate or substituted 5-pyrimidinyl borate are subjected to Suzuki coupling to obtain the product P.

[0037] Its synthetic route is as follows:

[0038]

[0039] Wherein, the ...

Embodiment 1

[0061] Example 1: 2-(4-morpholinyl)-4-(2-amino-5-pyrimidinyl)-6-(N-cyclopropyl-N-(1-(3-fluorobenzoyl)- Synthesis of 4-piperidinyl))amino-1,3,5-triazine (compound 1)

[0062] step one:

[0063]

[0064] Acetone (15mL) and 2,4,6-trichloro-1,3,5-triazine (0.61g) were added to a round bottom flask, cooled to -10°C, and 4-cyclopropylamino-1-( A mixture of 3-fluorobenzoyl)piperidine (0.90 g), triethylamine (TEA, 0.46 mL) and acetone (15 mL). After the addition was complete in about 30 minutes, the acetone was removed under reduced pressure, and water (10 mL) was added to the residue, which was extracted twice with dichloromethane (20 mL). The extract was dried over anhydrous sodium sulfate, and the solvent was removed to obtain intermediate M1 (oil).

[0065] Step two:

[0066]

[0067] Intermediate M1, morpholine, diisopropylethylamine and dichloromethane were added to a round bottom flask, and the mixture was stirred at room temperature for 1 hour. The reaction mixture ...

Embodiment 2

[0071] Example 2: 2-(4-morpholinyl)-4-(2-amino-5-pyrimidinyl)-6-(N-cyclopropyl-N-(1-(3-methylbenzoyl) Synthesis of -4-piperidinyl))amino-1,3,5-triazine (Compound 2)

[0072] Synthesis with compound 1. 4-Cyclopropylamino-1-(3-methylbenzoyl)piperidine was substituted for 4-cyclopropylamino-1-(3-fluorobenzoyl)piperidine. The total yield of the three steps is 44%. EI-MS: 516 (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 invention relates to 2-(4-morpholino)-4,6-disubstituted pyrimidine / s-triazine compounds, salts thereof, and an application of the compounds or the salts. The above disclosed 2-(4-morpholino)-4-(N-(1-benzoyl-4-piperidyl)amino)-6-(pyridyl or pyrimidinyl)pyrimidine or s-triazine compounds have a general formula shown in the description; and in the formula, X and Y are N or CH, R<1> is a C1-C3 alkyl group, R<2> is hydrogen, halogen, a methyl group or a trifluoromethyl group, R<3> is an amino group, a methoxy group, a cyano group or a trifluoromethyl group, and X is not N when the R<2> is hydrogen, R<3> is the amino group and Y is N. The compounds and the salts have PI3K and RAF kinase inhibition dual activity, can simultaneously inhibit a PI3K / AKT / mTOR signal transduction pathway and an Ras / RAF / MEK / ERK signal transduction pathway, and have good antitumor activity. The invention also discloses a use of the compounds of the general formula as a PI3K / / RAF dual inhibitor.

Description

technical field [0001] The invention belongs to the technical field of antineoplastic drugs, and specifically relates to 2-(4-morpholino)-4,6-disubstituted pyrimidine or s-triazine compounds, pharmaceutically acceptable salts and applications thereof. Background technique [0002] Cancer is one of the malignant diseases that seriously threaten human health. In the past 30 years, the incidence of cancer in my country has been in a period of rapid rise. The incidence of cancer is about 2 million per 100,000 people. Every year, there are more than 3.2 million new cases, about 2.7 million deaths, and more than 7 million patients under treatment. [0003] At present, the main treatment methods for cancer are still surgical treatment, radiotherapy and drug treatment, but to a large extent, drug treatment is still the main treatment. Therefore, it is of great significance to research and develop new antitumor drugs. [0004] In recent years, with the progress of tumor molecular b...

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
IPC IPC(8): C07D401/14A61K31/5377A61P35/00
CPCC07D401/14
Inventor 张三奇汪慧岩曹永孝王瑾张浩辛敏行吕社民
Owner XI AN JIAOTONG UNIV
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