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

Dihydropyrimidine-triazole derivatives, preparation method and application thereof

A technology of triazoles and dihydropyrimidines, applied in the field of medicine, can solve problems such as poor water solubility, strong liver toxicity, and poor metabolic stability

Active Publication Date: 2020-05-29
SHANDONG UNIV
View PDF5 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, there are currently no drugs on the market for related targets
Aiming at the disadvantages of strong hepatotoxicity, poor water solubility and poor metabolic stability of current clinical candidate drugs, through the crystal complex structure of core protein and ligand, rational drug design based on target was carried out, and a novel class of dihydro Pyrimidine-triazole compounds, such compounds have no relevant reports in the prior art

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
  • Dihydropyrimidine-triazole derivatives, preparation method and application thereof
  • Dihydropyrimidine-triazole derivatives, preparation method and application thereof
  • Dihydropyrimidine-triazole derivatives, preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0041] Embodiment 1. Preparation of Compound 2

[0042] Take a 500mL round-bottomed flask, dissolve 2-thiazolecarboxamidine hydrochloride (2.00g, 12.22mmol) in 250mL absolute ethanol, and add 2-bromo-4-fluorobenzaldehyde (3.74g, 18.42mmol) successively at room temperature ), ethyl acetoacetate (1559μL, 12.22mmol), sodium acetate (1.66g, 12.22mmol), reflux at 80°C for 6h. After the reaction, cool to room temperature, remove absolute ethanol by rotary evaporation, add water (60mL), extract with ethyl acetate three times (25mL x 3), combine organic phases, wash with saturated brine three times (30mL x 3), anhydrous sodium sulfate Drying; concentration, dry loading, flash preparative chromatography on a silica gel column, recrystallization from a dichloromethane-n-hexane mixed solvent to obtain 3.98 g of a yellow solid with a yield of 76%; melting point 153-156°C.

[0043]

[0044]Compound 2 spectral data: 1 H NMR (400MHz, CDCl 3 )δ7.81(d, J=2.8Hz, 1H), 7.46(s, 1H), 7.38–7.2...

Embodiment 2

[0045] Embodiment 2. Preparation of compound 3

[0046] Take a 500mL round bottom flask, dissolve Intermediate 2 (2.00g, 4.71mmol) in 200mL carbon tetrachloride, slowly add NBS (0.88g, 4.94mmol), and react at reflux at 50°C for 10h. After the reaction, cool to room temperature, remove carbon tetrachloride by rotary evaporation, add water (50mL), extract with ethyl acetate three times (20mL x 3), combine organic phases, wash with saturated brine three times (25mL x 3), anhydrous sulfuric acid Drying over sodium; concentration, dry loading, flash preparative chromatography on a silica gel column, recrystallization from a dichloromethane-n-hexane mixed solvent to obtain 1.21 g of a yellow solid with a yield of 51%; melting point 123-128°C.

[0047]

[0048] Spectral data of compound 1: 1 H NMR (400MHz, CDCl 3 )δ7.84(d,J=3.1Hz,1H),7.52(s,2H),7.44–7.35(m,1H),7.32(dd,J=8.1,2.6Hz,1H),7.02(t,J =8.0Hz,1H),6.09(s,1H),4.94(d,J=8.9Hz,1H),4.61(s,1H),4.09(d,J=7.0Hz,2H),1.16(t,J =7.1H...

Embodiment 3

[0049] Embodiment 3. Preparation of compound 4

[0050] Take a 100mL round bottom flask, dissolve intermediate X-3 (0.89g, 1.77mmol) in 45mL acetone, add NaN 3 (0.23g, 3.54mmol), stirred overnight at room temperature. After the reaction, cool to room temperature, remove carbon tetrachloride by rotary evaporation, add water (50mL), extract with ethyl acetate three times (20mL x 3), combine organic phases, wash with saturated brine three times (25mL x3), anhydrous sodium sulfate Drying; concentration, dry loading, flash preparative chromatography on a silica gel column, recrystallization from a dichloromethane-n-hexane mixed solvent to obtain 0.85 g of a yellow solid, yield 91%; melting point 123-126°C.

[0051]

[0052] Compound 4 spectral analysis data: 1 H NMR (400MHz, CDCl 3 )δ8.64(s,1H),7.85(d,J=3.1Hz,1H),7.55(d,J=3.1Hz,1H),7.48–7.37(m,1H),7.35–7.29(m,1H ),7.10–6.92(m,1H),6.29–6.02(m,1H),4.97(s,1H),4.60(d,J=2.6Hz,1H),4.17–4.00(m,2H),1.13( t,J=7.1Hz,3H); 13 C NMR (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

PropertyMeasurementUnit
melting pointaaaaaaaaaa
melting pointaaaaaaaaaa
melting pointaaaaaaaaaa
Login to View More

Abstract

The invention discloses a dihydropyrimidine-triazole derivative, a preparation method therefor and an application of the dihydropyrimidine-triazole derivative. The compound has a structure represented by a formula I shown in the description. The invention further relates to the preparation method for the compound with the structure represented by the formula I and a pharmaceutical composition and provides the application of the compound in preparation of anti-HBV drugs.

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to dihydropyrimidine-triazole derivatives, a preparation method thereof and a pharmaceutical use thereof. Background technique [0002] Viral hepatitis type B (viral hepatitis type B), referred to as hepatitis B (Hepatitis B), is a major infectious disease caused by hepatitis B virus (HBV), long-term development can lead to acute and chronic viral hepatitis, severe hepatitis, liver cirrhosis and primary hepatocellular carcinoma (hepatocellular carcinoma, HCC). According to the report of the World Health Organization (WHO), nearly 2 billion people in the world have been infected with HBV, of which about 240 million people are chronic HBV infected people, and an average of about 780,000 people die each year from acute and chronic hepatitis and related complications caused by HBV infection. disease. The drugs currently used to prevent and treat chronic hepatitis B (CHB) ...

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): C07D417/14A61K31/506A61P31/20
CPCC07D417/14
Inventor 刘新泳贾海永展鹏俞霁
Owner SHANDONG UNIV
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