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Diaryl benzo pyridine derivative, and preparation and use thereof

A technology of benzopyrimidine and diaryl, which is applied in the application and preparation field of related drugs, and achieves the effects of low cytotoxicity, novel structure and simple preparation method

Inactive Publication Date: 2009-06-24
FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

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

Method used

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  • Diaryl benzo pyridine derivative, and preparation and use thereof
  • Diaryl benzo pyridine derivative, and preparation and use thereof
  • Diaryl benzo pyridine derivative, and preparation and use thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0041] Embodiment 1: Synthesis of diarylbenzopyrimidine derivatives (method 1)

[0042] Under the protection of an inert gas, add substituted phenol (or aniline, etc.) 2 CO 3 , control the temperature at 80-120°C, and stir for 8-12 hours. After TLC showed that the reaction was finished, the K 2 CO 3, the filtrate was poured into cold water, the precipitated solid was filtered and dried. Decolorized by activated carbon and recrystallized from toluene to obtain the desired compound.

[0043] With different 4-chlorobenzopyrimidine derivatives and different substituted phenols (or aniline, etc.). The target compound was prepared respectively by the above method, and some results are as follows:

[0044] Under N2 protection, 2-methylphenol (4.2mmol) was added to 30mL of anhydrous DMF, stirred to dissolve it, and then 2-(4-cyanoanilino)-4-chlorobenzopyrimidine (3.5mmol ), stirred for 10min to dissolve it, added anhydrous K 2 CO 3 (0.021mol), the temperature was controlled a...

Embodiment 2

[0058] Example 2: Synthesis of diarylbenzopyrimidine derivatives (method 2)

[0059] Mix 2-methoxyphenol and 2-chlorobenzopyrimidine derivatives together, heat to 150-210°C until the reactants are completely melted, and react for 1 hour. TLC showed that after the reaction was completed, it was dissolved in DMF, decolorized by activated carbon, filtered, and the filtrate was poured into cold water, and the precipitated solid was filtered and dried. Recrystallization from toluene afforded the desired compound.

[0060]

[0061] White flocculent solid, yield 82.9%; melting point: 220.0-220.5°C; 1 H NMR (DMSO-d 6 ) δ (ppm) 3.73 (s, 3H, CH 3 O), 7.10(td, 1H, J=7.6Hz, J`=1.6Hz, Ar`H 6 ), 7.30 (dd, 1H, J=8.4Hz, J`=1.2Hz, Ar`H 3 ), 7.35-7.41 (m, 2H, Ar`H 4，5 ), 7.47 (td, 1H, J=8.0Hz, J`=0.8Hz, ArH 7 ), 7.56(d, 2H, J=8.8Hz, Ar``H 2，6 ), 7.71 (d, 1H, J=8.4Hz, ArH 6 ), 7.84(d, 2H, J=8.8Hz, Ar``H 3，5 ), 7.89 (td, 1H, J=8.4Hz, J`=1.2Hz, ArH 8 ), 8, 22 (d, 1H, J=8.4Hz, ArH 9 ...

Embodiment 3

[0076] Example 3 Anti-HIV biological activity test

[0077] 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 IC 50 , Toxicity determination is carried out in parallel with anti-HIV activity experiment, also in MT-4 cell culture, the concentration that makes 50% uninfected cells take place cytopathic (CC 50 ), and calculate the selectivity index SI=CC 50 / IC 50 .

[0078] Materials and Methods:

[0079] The anti-HIV activity of each compound is monitored by the inhibitory effect of the drug on the...

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Abstract

The invention belongs to the medicine technical field, and provides a series of diaryl benzo pyrimidine derivatives (DABPs) of formula I, pharmaceutical salt thereof, stereochemical isomers thereof, a hydrate and a solvolyte thereof, a polycrystal and an eutectic crystal thereof, a precursor and a derivative thereof with the same biological function, a preparation method thereof and application of a composition containing one or a plurality of the compounds to related medicines for treating AIDS and the like. The results of pharmacological experiments prove that the compounds have obvious anti-HIV-1 virus activity, can effectively inhibit replication of MT-4 cells infected by the HIV-1 virus, and have low cytotoxicity.

Description

technical field [0001] The present invention belongs to the technical field of medicine, and specifically relates to the pharmaceutically acceptable salts of diarylbenzopyrimidine derivatives described in general formula I, their hydrates and solvates, their polycrystals and cocrystals, their precursors with the same biological function and Derivatives, their preparation methods and the application of compositions containing one or more such compounds in the treatment of AIDS and other related drugs, their preparation methods and uses. Background technique [0002] AIDS (AIDS) or Acquired Immune Deficiency Syndrome (Acquired Immune Deficiency Syndrome) is an epidemic infectious disease caused by Human Immunodeficiency Virus (Human Immunodeficiency Virus, HIV). [0003] Studies have shown that 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 t...

Claims

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Application Information

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IPC IPC(8): C07D239/94A61K31/517A61P31/18
Inventor 陈芬儿曾兆森梁永宏
Owner FUDAN UNIV
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