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

Triazole compounds and preparation method and application thereof

A kind of compound, technology of triazole

Inactive Publication Date: 2019-09-24
SHANDONG UNIV
View PDF3 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the inventors found that because the chemical structure of JQ1 is similar to that of benzodiazepine sedative-hypnotics, it has side effects such as high neurotoxicity, poor water solubility, and high cytotoxicity, which limits the possibility of making it into a drug.

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
  • Triazole compounds and preparation method and application thereof
  • Triazole compounds and preparation method and application thereof
  • Triazole compounds and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0100] Example 1 Compound preparation

[0101] The synthetic route of compound of the present invention is as follows:

[0102]

[0103] The reagents used in the above preparation process are: (a) triethyl orthoacetate, 130 ° C; (b) sodium carbonate; tetrakis (triphenylphosphine) palladium; 2-fluoro-5-nitrophenylboronic acid, 1, 4-dioxane and water; 95°C; (c) cesium carbonate with R 2 , R 3 Substituent phenol, DMSO, 100°C; (d) 10% palladium carbon / H 2 ; methanol, room temperature; (e) pyridine, containing R 1 Sulfonyl chloride or acid chloride of the substituent, dichloromethane, 0°C to room temperature.

[0104] (1) Intermediate 2: Preparation of 6-bromo-3-methyl-[1,2,4]triazolo[4,3-a]pyridine

[0105] Dissolve 1.87g (10mmol) of 2-hydrazino-5-bromopyridine in 50mL of triethyl orthoacetate, raise the temperature to 130°C for 1 hour, pour the mixture into 100mL of ice water, and extract with ethyl acetate (60mL×3) Extract, combine the organic phases, dry the organic...

Embodiment 2

[0172] Example 2 : Detection of inhibitory activity of compounds on BRD4 protein

[0173] The inhibitory activity of compounds on BRD4 was detected by Homogeneous Time-Resolved Fluorescence (HTRF). The specific principles and experimental methods are as follows:

[0174] Experimental principle: HTRF combines the advantages of fluorescence resonance energy transfer FRET and time-resolved fluorescence TRF, and combines the homogeneous experimental method of FRET with the low background characteristics of TRF. It has the advantages of simple operation, high sensitivity, large throughput, The experimental data is stable and reliable.

[0175] Experimental procedure: Compounds were diluted with DMSO. Use the Diluent Buffer in the kit to dilute BRD4 (BD2, BD2) and Biotin-labeled histone H4 peptide, and prepare the reaction solution. Use DtectionBuffer in the kit to dilute Anti-GST-TB 2+ Cryptate and SA-XL-665, and configure the detection solution. Take a 384-well plate and ar...

Embodiment 3

[0183] Example 3 : EC of compound in J-Lat HIV-1 latent virus infected cell line 50

[0184] Experiment principle: EC 50 is the half-maximal effect concentration, which refers to the concentration of the compound when the compound reaches 50% effect of activating HIV latent virus activity, and the unit is μM.

[0185] Experimental procedure: Take the well-grown pseudovirus-infected J-Lat cells and spread them in a 96-well transparent plate. The amount of cells used is 2×10 per well. 5 Each, add different concentrations of the test compound (prepared according to the method of Example 1) respectively, the final concentrations are respectively 320, 160, 80, 40, 20, 10, 5, 0 μ M, JQ1 is the positive control group, and the untreated group is negative For the control, at least 3 replicate wells for each concentration, and each experiment was repeated 3 times. at 5% CO 2 After culturing in the incubator for 24 hours, the cells were collected by centrifugation, the supernatant ...

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 provides triazole compounds and a preparation method and application thereof. The provided triazole compounds or pharmaceutically acceptable salts thereof have the structure shown as a formula (I), wherein R1, R2 and R3 are respectively and independently selected from -SO2R4, -SO2R5, COR6, H, and halogen; R4, R5 and R6 are respectively and independently selected from an aryl group, a heteroaryl group, a linear or branched alkyl group, an alkenyl group and a cycloalkyl group, wherein the aryl group, the heteroaryl group, the linear or branched alkyl group, the alkenyl group and the cycloalkyl group are unsubstituted or substituted by R7; R7 is selected from halogen, a C1-5 straight or branched alkyl group, a haloalkyl group, a C1-5 straight or branched alkoxy group and a nitro group. The compounds have good inhibitory activity against BRD4, HIV latent virus infection activation activity, low toxicity, high druggability and a more potential clinical application value.

Description

technical field [0001] The invention relates to the technical field of medicine, in particular to triazole compounds and their preparation methods and applications. Background technique [0002] The information disclosed in this background section is only intended to increase the understanding of the general background of the present invention, and is not necessarily taken as an acknowledgment or any form of suggestion that the information constitutes the prior art already known to those skilled in the art. [0003] Human immunodeficiency virus (Human Immunodeficiency Virus, HIV), also known as AIDS virus, is a retrovirus that can cause defects in the human immune system. After entering the human body, it mainly attacks T lymphocytes, blocks cellular immunity and humoral immunity, causes the immune system to collapse, causes the spread of various diseases, and eventually leads to AIDS (AIDS), which poses a great threat to human health and social stability. Due to the lack o...

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): C07D471/04A61K31/437A61P31/18
CPCA61P31/18C07D471/04
Inventor 李荀于海鹏郑永唐黄旭升
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