28th International Conference on Antiviral Research location:Rome, Italy date:11-15 May 2015
The recent outbreaks of the highly pathogenic avian A/H5N1 and pandemic A/H1N1/2009 influenza viruses have emphasized the
need for anti-influenza drug discovery. The piperidine nucleus is an attractive drug template exploited in agents with applications
as anti-histaminic, anti-inflammatory, fungicidal, bactericidal, anticancer, analgesic, CNS stimulant and or anti-depressant activities.
In an effort to discover novel compounds as potential anti-influenza drugs, several molecules of our diverse in-house library
were screened for anti-influenza virus activity. Following this approach, we identified disubstituted piperidine-based compounds
as interesting hit compounds that display low micromolar activity against the influenza A/PR/8/34 virus (A/H1N1) in cell culture.
To investigate the structure-activity relationships, several analogues were easily synthesized by a one-step Ugi four-component
reaction from an amine, an isocyanide, N-substituted piperidones and carboxylic acid components. Time-of-addition studies
showed that the compounds act during influenza virus entry. Mechanistic studies are ongoing to precisely identify their antiviral
target, and explain the basis for the observed H1N1 specificity.