Check patentability & draft patents in minutes with Patsnap Eureka AI!

Triazolopyrimidine derivative as well as preparation method and application thereof

A technology for pyrimidine and derivatives, which is applied in the field of triazolopyrimidine derivatives and their preparation, and can solve problems such as research on USP28 inhibitors in the clinical stage

Active Publication Date: 2022-07-29
ZHENGZHOU UNIV
View PDF7 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, there are few reports on USP28 inhibitors, and no USP28 inhibitors have yet entered the clinical stage of research

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
  • Triazolopyrimidine derivative as well as preparation method and application thereof
  • Triazolopyrimidine derivative as well as preparation method and application thereof
  • Triazolopyrimidine derivative as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036] The triazolopyrimidine derivatives of this embodiment are compounds of the general formula I, in the general formula I, R 1 is cyclopropyl. This triazolopyrimidine derivative is referred to as compound 1. The preparation method of compound 1 is as follows:

[0037] 1) Synthesis of compound C, compound A (50.0 g, 1.02 eq.) and compound B (75.6 g, 1.0 eq.) were placed in a 5L autoclave, and 750 mL of ethanol was added to form a suspension. Under stirring, triethylamine (62.50 g, 3.0 eq.) was added to the suspension, heated to 125° C., and kept stirring for 30 h. After cooling to room temperature, the reaction was monitored by TLC (PE:EA=1:1). Most of the solvent was distilled off under reduced pressure, ethyl acetate and water were added, and 6M hydrochloric acid solution was added under stirring to adjust the pH of the aqueous phase to 5. After standing to separate layers, the organic phase was washed three times with water and once with saturated brine. The organic...

Embodiment 2～38

[0041] The triazolopyrimidine derivatives of Examples 2 to 38 all have the general formula I, R 1 Selected in order from cyclohexyl, 4-methylpiperidyl, 4-methylpiperazinyl, n-propyl, 2-hydroxyethyl, 2-methoxyethyl, 2-aminoethyl, 2-(acetyl amino)ethyl, 2-(phenylamino)ethyl, 2-(benzoate amino)ethyl, 2-(tert-butoxycarbonylamino)ethyl, 2-(dimethylamino)ethyl base, 2-(tert-butoxycarbonylmethylamino)ethyl, (2-(4-phenylpiperazin-1-yl)ethyl, benzyl, 4-pyridyl, 2-fluorobenzyl, 2- chlorobenzyl, 2-bromobenzyl, 2-methylbenzyl, 2-methoxybenzyl, 3-fluorobenzyl, 3-chlorobenzyl, 3-bromobenzyl, 3-methylbenzyl, 3-methoxybenzyl, 4-fluorobenzyl, 4-chlorobenzyl, 4-bromobenzyl, 4-methylbenzyl, 4-methoxybenzyl, 4-trifluoromethylbenzyl, 3,5-dimethoxybenzyl, 4-methoxyphenyl, 4-chlorophenyl, 2,3-dihydro-1H-inden-1-yl, benzo[d][1,3] Dioxolane-4-yl, the obtained triazolopyrimidine derivatives are sequentially denoted as compounds 2 to 38. The preparation methods of compounds 2 to 38 are basically the ...

Embodiment 39

[0080] The triazolopyrimidine derivatives of this embodiment are compounds of the general formula II, in the general formula II, R 2 is cyclopropyl. This triazolopyrimidine derivative is designated as compound 39. The specific preparation method of compound 39 is as follows: wherein, step 1) synthesis of compound C, step 2) synthesis of compound D is the same as that of Example 1.

[0081] 3) Synthesis of compound E: put the intermediate compound D (200mg, 1.0eq.) in a 25mL thick-walled eggplant-shaped flask, dissolve in anhydrous acetonitrile, and add N,N-diisopropylethylamine (92mg, 1.5 eq.). Under the ice bath, amine substance - cyclopropylamine (40mg, 1.5eq.) was added dropwise. The mixture was stirred at room temperature for 8 h, and after the reaction was monitored by TLC (PE:EA=2:1), the solvent was distilled off under reduced pressure. It was extracted three times with ethyl acetate and washed once with water. The organic phase was dried over anhydrous sodium sulf...

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 belongs to the field of medicinal chemistry, and particularly relates to a triazolopyrimidine derivative as well as a preparation method and application thereof. The triazolopyrimidine derivative is a compound with a general formula I, a general formula II or a general formula III, a general formula I, a general formula II and a general formula III are shown in the specification. The triazolopyrimidine derivative disclosed by the invention is novel in structure. A USP28 inhibitory activity test proves that the compound disclosed by the invention has a relatively good inhibitory ability on USP28, so that the compound has a good potential antitumor drug application value, and a brand new drug choice can be provided for developing inhibitors or antitumor drugs based on USP28 targets.

Description

technical field [0001] The invention belongs to the field of medicinal chemistry, in particular to a triazolopyrimidine derivative and a preparation method and application thereof. Background technique [0002] The human genome encodes nearly 100 deubiquitinating enzymes (DUBs). The deubiquitinating enzyme family is divided into six categories according to sequence and domain conservation: USPs (ubiquitin-specific proteases), UCHs (ubiquitin carboxy-terminal hydrolases), OTUs (ovarian tumor-like proteases), MJDs (Machado-Josephin domain proteases), JAMMs (MPN(+) / JAMM proteases) and MINDYs (MINDYs proteases). Studies have found that dysregulation of protein ubiquitination can lead to the development of various diseases, such as tumors, neurodegenerative diseases, and inflammation. Therefore, targeting the ubiquitination signaling pathway can be used as a therapeutic approach for related diseases. [0003] In 2001, researchers first discovered and identified ubiquitin-speci...

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): C07D487/04A61P35/00
CPCC07D487/04A61P35/00Y02P20/55
Inventor 刘宏民孙凯张怡秋刘珍珍
Owner ZHENGZHOU 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