L-leucine derivatives blocking entrance of H5N1 avian influenza virus and preparation method for same

Abstract

The invention discloses L-leucine derivatives blocking the entrance of H5N1 avian influenza virus, which are 3,4-dyhydroxyl benzoyl leucine methyl ester and 3,4-dyhydroxyl phenylacetyl leucine methyl ester. The 3,4-dyhydroxyl benzoyl leucine methyl ester is prepared by condensing 3,4-dyhydroxyl benzoic acid with L-leucine methyl ester; the 3,4-dyhydroxyl phenylacetyl leucine methyl ester is prepared by taking 3,4-dyhydroxyl phenylacetic acid as a starting material, treating the 3,4-dyhydroxyl phenylacetic acid by virtue of dimethyl sulphate and thionyl chloride sequentially, then condensing the 3,4-dyhydroxyl phenylacetic acid with L-leucine methyl ester, and then performing demethylation reaction. The compounds, namely, the 3,4-dyhydroxyl benzoyl leucine methyl ester and the 3,4-dyhydroxyl phenylacetyl leucine methyl ester, disclosed by the invention, have a strong inhibitory activity on Influenza strain A/Vietnam/1194/2004 avian influenza virus, and have a mechanism of acting on the entrance phase of H5N1 virus infected cells; and the compounds are a new inhibitor resisting the entrance of avian influenza virus, and can be used as a medicine for preventing or treating H5N1 avian influenza.

Description

technical field [0001] The invention belongs to the field of medicinal chemistry and relates to 5 N 1 L-leucine derivatives for avian influenza virus entry and preparation methods thereof. Background technique [0002] Since the first human case of avian influenza infection H 5 N 1 Since the death case was reported in Hong Kong, China in 1997, the virus had spread in 7 countries including China, Vietnam, and Thailand by March 2006, and 176 cases had been infected with H 5 N 1 At least 97 people died in patients with type 1 avian influenza virus, and the mortality rate was 55%, which was characterized by high pathogenicity and high mortality. The type A highly pathogenic avian influenza virus currently circulating in my country is H 5 N 1 Subtype. Today, the world is facing the danger of an avian influenza pandemic. Be wary of possible antigenic mutation of avian influenza virus, or genetic reassortment between the avian influenza virus and the current influenza A vi...

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Problems solved by technology

[0004] In antiviral screening experiments, we found that 3,4-dihydroxybenzoic acid and 3,4-dihydroxyphenylacetic acid had no obvious anti-H 5 N 1 active, but modified with L-leucine methyl ester, respectively, have some anti-H 5 N 1 effect, and the results of Time-of-addition assay show that the new compound acts on H 5 N 1 The virus enters the stage of cell infection; the hemagglutinin inhibition experiment further shows that the new compound does not act on the hemagglutinin HA1 subunit, but may act on the HA2 subunit. These results indicate that the new compound may be a new anti-inflammatory agent. h 5 N 1 Entry inhibitor, can be used as a lead compound for further research, there is no relevant research report yet

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