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

Piperidine-4-amido diaryl pyrimidine derivative as well as preparation method and application thereof

A technology of aminodiarylpyrimidine and derivatives, applied in the field of medicine, to achieve strong anti-HIV-1 virus activity, enhanced binding force, and small cytotoxic effects

Inactive Publication Date: 2015-07-29
FUDAN UNIV
View PDF2 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Classic NNRTIs only work on HIV-1, but not HIV-2, study shows

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
  • Piperidine-4-amido diaryl pyrimidine derivative as well as preparation method and application thereof
  • Piperidine-4-amido diaryl pyrimidine derivative as well as preparation method and application thereof
  • Piperidine-4-amido diaryl pyrimidine derivative as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0027] Embodiment 1: the synthesis of final product I

[0028] Add potassium carbonate to 0 of N,N-dimethylformamide of secondary amine II oC solution, stirred for 0.5h, and added dropwise the N,N-dimethylformamide solution of α-bromoacetanilide Ⅲ, and continued at 0 oC Under stirring for 2h, then rose to room temperature and stirred for 9h. TLC showed the reaction was complete. Pour into water, filter, wash with water, and filter with suction. Dry and recrystallize from toluene to give the desired solid.

[0029] The target compounds were obtained by using different α-bromoacetanilide III by the above method, and some results are as follows:

[0030] Potassium carbonate (17 mmol) was added to the N of 3,5-dimethyl-4-{[2-(piperidin-4-amino)pyrimidin-4-yl]oxy}benzonitrile II (8.5 mmol) , N-dimethylformamide (25 mL) of 0 oC solution, stirred for 0.5h, and added dropwise a solution of 2-bromo-N-acetanilide III (8.5 mmol) in N,N-dimethylformamide (10 mL). oC Under stirr...

Embodiment 2

[0083] Embodiment 2: anti-HIV biological activity test

[0084] The anti-HIV virus activity at the cell level in vitro was determined by the Rega Institute of Pharmacy at Katholleke University in Belgium, mainly including two aspects: inhibitory activity and cytotoxicity to HIV-infected MT-4 cells. The method is as follows: make the compound in HIV-infected MT-4 cells, at different times of HIV infection, use the MTT method to measure the protective effect of the drug on HIV-induced cytopathy, and calculate that 50% of the cells are free from HIV-induced cytopathy half effective concentration EC 50 , the toxicity assay was carried out in parallel with the anti-HIV activity experiment, also in MT-4 cell culture, the concentration that caused 50% of uninfected cells to undergo cytopathic changes was determined by MTT method (CC 50 ), and calculate the selectivity index SI = CC 50 / EC 50 .

[0085] Materials and Methods:

[0086] The anti-HIV activity of each compound is mon...

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 technical field of medicines, in particular to a piperidine-4-amido diaryl pyrimidine derivative shown as the general formula I, and pharmaceutical salt, hydrates and solvate, polycrystal or an eutectic crystals, precursors and derivatives, having the same biological functions with the piperidine-4-amido diaryl pyrimidine derivative, of the piperidine-4-amido diaryl pyrimidine derivative, as well as a preparation method and application of a composition containing one or more chemical compounds of this kind in related drugs for treating aids and the like. Pharmacological experimental results prove that the compounds have remarkable anti-HIV-1 virus activity, can effectively inhibit replication of HIV-1 virus infected MT-4 cells, and have relatively low cytotoxicity.

Description

technical field [0001] The invention belongs to the technical field of medicine, and specifically relates to piperidine-4-aminodiarylpyrimidine derivatives and their preparation methods and uses. Background technique [0002] AIDS (Acquired immune deficiency syndrome) is an epidemic infectious disease caused by human immunodeficiency virus (Human immunodeficiency virus, HIV). [0003] Reverse transcriptase (Reverse transcriptase, RT) plays a decisive role in the process of HIV reverse transcription from mRNA to DNA, so it has become one of the important targets for anti-AIDS drug design. [0004] In the existing anti-HIV drug research, non-nucleoside reverse transcriptase inhibitors (NNRTIs) have become one of the hotspots of medicinal chemists in various countries because of their high efficiency and low toxicity. Currently, there are five anti-HIV reverse transcriptase inhibitors approved by the US FDA: Nevirapine, Delavirdine, Efavirenz, Etravirine, Rilpivirine. In add...

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): C07D401/12A61K31/506A61K31/635A61P31/18
CPCC07D401/12
Inventor 陈芬儿万正勇
Owner FUDAN 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