6-QUINOXALINAMINE DERIVATIVES AS INHIBITORS OF THE NEURAMINIDASE OF THE INFLUENZA A H1N1 VIRUS.

摘要

The present invention is intended to find novel Hemagglutinin (HA) and neuraminidase (NA) inhibitors of influenza A H1N1 virus, which is based on the search of fragments. The invention refers to compounds pertaining to the biotechnological field which have antiviral activity, particularly against Influenza A H1N1. The compounds are based on principles for designing drugs by fragments search; the scrutiny of the Maybridge Library Ro3 of 1000 chemical compounds was performed, evaluating the effect of the compounds over the HA and NA of the human influenza virus. The recombinant neuraminidase was incubated with the compounds, stimulating the inhibition of the enzyme activity, detecting the fluorescent product of the reaction, where the scrutiny of the HA, was performed for determining the inhibition of the Hemagglutinin activity of the influenza virus upon being incubated with the compounds. The influenza A H1N1 virus Mexico/2009 used in the essays was produced in cells MDCK growing over microcarriers suspended in a serum-free medium. Five HA inhibiting compounds were found as well as thirteen NA inhibiting compounds. The 1-azepanyl (3 piperidinyl) methanone (AzPM) compound and the 6-aminoquinoxaline (AQA) compound with activity over the NA, were consciously studied. The identity and purity of the Az PM were confirmed by the RMN of 13C. The AzPM was confirmed as inhibitor of recombinant NA. In addition, it was found that the NA inhibition performed by the AzPM is reduced in the presence of calcium, since it is intended to maintain the thermal stability and the quaternary structure of the NA. The AQA compound at 95% was confirmed as a NA inhibitor in the context of the influenza A H1N1 virus.