Compound of amide diketone acid, preparation method and application

Abstract

This invention relates to a method for preparing amide diketonic acids and their pharmaceutical application. The general structure of amide diketonic acids is shown in formula 1, wherein, R' is one or two of H, F, Cl, Br, methyl, methoxy and hydroxyl; R1 is one of H, F, Cl, methyl, methoxy and hydroxyl; R1 is one of H, F, Cl, methyl, methoxy and hydroxyl; R2 is one of H, F, Cl, Br, methyl, methoxy and nitro; R3 is one of H, methoxy and hydroxyl; R4 is one of H, F, Cl, Br, methyl, methoxy and nitro; R5 is one of H, F, Cl, methyl, methoxy and hydroxyl. The method comprises: reacting carboxylic acids and thionyl chloride to synthesize acyl chlorides, reacting with m-aminoacetophenone to obtain N-(3-acetylphenyl)-amide compounds, reacting with diethyl oxalate in the presence of sodium methoxide, and hydrolyzing to obtain amide diketonic acid compounds. The amide diketonic acid compounds can be used to prepare antiviral drugs, especially anti-AIDS drugs.

Description

technical field The invention relates to diketoacid compounds and a preparation method thereof, in particular to amide diketoacid compounds, a preparation method and pharmaceutical use thereof. Background technique Human immunodeficiency virus (human immunodeficiency virus, HIV) is the pathogen of AIDS (acquired immune deficiency syndrome, AIDS), divided into HIV-1 and HIV-2 types. HIV-1 is prevalent throughout the world, while HIV-2 is mainly confined to the West African region. HIV-1 replication requires three key enzymes: reverse transcriptase, protease and integrase. The current drugs for the treatment of AIDS mainly target reverse transcriptase and protease, preventing the reverse transcription of single-stranded RNA virus or curbing the cleavage of viral protein and the release of mature virus. Because reverse transcriptases and proteases are highly mutable, the efficacy of these drugs is limited by the rapid emergence of resistance. Antiviral combination therapy (c...

AI Technical Summary

Problems solved by technology

The efficacy of these drugs is limited by the rapid emergence of resistance due to the high susceptibility of reverse transcriptases and proteases to mutations

Antiviral combination therapy (combination therapy) (see De clercq E. Biochim Biophys Acta, 2002, 1587 (2-3): 258-275), that is, combined use of reverse transcriptase inhibitors and protease inhibitors for treatment, can be used in In the short term, the virus in the patient's blood is rapidly reduced to an undetectable level, but the side effects of the drug itself and the interaction between the drugs make it difficult for the patient to tolerate for a long time, which limits the application of these drugs

Fusion inhibitors are recently listed anti-HIV drugs, which block HIV-1 from entering host cells by inhibiting virus and cell fusion (see Fung HB, Guo Y. ClinTher, 2004, 26 (3): 352-378.), but It is expensive and cannot completely eradicate the virus in the body, so it is necessary to find drugs that act on new targets of the virus

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