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Diarylpyrimidine derivative containing biphenyl structure and preparation method and application thereof

A technology of diaryl pyrimidine and biphenyl structure, applied in the field of medicine, can solve the problem of drug loss of activity, and achieve the effects of low cytotoxicity, high selectivity coefficient, and strong biological activity

Inactive Publication Date: 2018-12-21
FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, amino acid mutations on reverse transcriptase can inactivate the originally effective drug, that is, produce drug-resistant HIV strains

Method used

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  • Diarylpyrimidine derivative containing biphenyl structure and preparation method and application thereof
  • Diarylpyrimidine derivative containing biphenyl structure and preparation method and application thereof
  • Diarylpyrimidine derivative containing biphenyl structure and preparation method and application thereof

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] Embodiment 1: the synthesis of final product I

[0027] Add compound III and base into the solvent, stir for 30 min, then add compound II, stir at 30-100° C. for 4-10 h. The reaction was monitored by TLC until the starting material was consumed completely. The reaction solution was poured into ethyl acetate, washed with water and saturated brine successively, and the organic phase was dried over anhydrous sodium sulfate overnight. After filtration, concentration, and recrystallization from ethyl acetate and petroleum ether, the desired solid was obtained.

[0028] The target compounds were obtained by using the above methods with raw materials containing different substituents, and some results are as follows:

[0029] 4'-Hydroxy-3',5'-dimethyl[1,1'-biphenyl]-4-cyanocyanide (4.48mmol) and potassium carbonate (6.72mmol) were added to N,N-diphenyl Methylformamide (20 mL), stirred for 30 min, then added 2-(4-chlorophenyl)amino-4-chloropyrimidine (4.93 mmol), stirred at ...

Embodiment 2

[0058] Embodiment 2: anti-HIV biological activity test

[0059] 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: 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 time of HIV infection, use the MTT method to measure the protective effect of the drug on the cytopathy induced by HIV mutagenesis, and calculate that 50% of the cells are free from HIV-induced cytopathy half effective concentration EC 50 , the toxicity assay is carried out in parallel with the anti-HIV activity experiment, also in MT-4 cell culture, the concentration (CC 50 ), and calculate the selectivity index SI=CC 50 / EC 50 .

[0060] Materials and Methods:

[0061] The anti-HIV activity of each compound is monitored by the inhibitory effect of the drug on the cytopathic effect caused by HIV in cells....

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Abstract

The invention belongs to the technical field of medicines, and particularly relates to a diarylpyrimidine derivative containing a biphenyl structure and a preparation method and application thereof. The compound structure disclosed by the invention relates to the diarylpyrimidine derivative containing the biphenyl structure shown as general formula I, and the invention further relates to a medicinal salt, a hydrate and a solvate thereof, a polycrystal or a co-crystal thereof, a precursor and a derivative with the same biological function thereof, a preparation method thereof and application ofa composition containing one or more of such compounds in related drugs for treating AIDS and the like. An in-vitro cell-level anti-HIV-1 activity experiment result shows that such small molecules have high anti-HIV-1 bioactivity, the replication of viruses in MT-4 cells infected by HIV-1 viruses can be notably inhibited, and moreover, cytotoxicity is low. (The general formula I is shown in the description.).

Description

technical field [0001] The invention belongs to the technical field of medicine, and specifically relates to a diarylpyrimidine derivative containing a biphenyl structure and a preparation method and application thereof. Background technique [0002] Acquired immunodeficiency syndrome (AIDS), which is caused by human immunodeficiency virus (Human immunodeficiency virus, HIV) infection, can lead to human immunodeficiency and a series of infections, which is a very harmful disease. infectious disease. More than 35 million people have died since the U.S. Centers for Disease Control (CDC) confirmed the first case in 1981. [0003] Reverse transcriptase (Reverse transcriptase, RT) plays a key role in the life cycle of HIV virus replication, responsible for the reverse transcription of viral RNA into DNA-RNA hybrids and the degradation of RNA in hybrids to form single-stranded viral DNA, which is then integrated Enzymes integrate viral DNA into host cells, so reverse transcripta...

Claims

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Application Information

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IPC IPC(8): C07D239/47A61K31/505A61P31/18
CPCA61P31/18C07D239/47
Inventor 陈芬儿桑亚丽孟歌韩胜
Owner FUDAN UNIV
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