New 4‑Acyl-1-phenylaminocarbonyl-2-phenylpiperazine Derivatives as Potential Inhibitors of Adenovirus Infection. Synthesis, Biological Evaluation, and Structure–activity Relationships

The
search for human adenovirus (HAdV)-specific antiviral drugs for the
treatment of HAdV infections in immunocompromised patients continues
to be a challenging goal for medicinal chemistry. Here, we report
the synthesis, biological evaluation, and structure–activity
relationships of a small molecules library. We have identified six
phenylpiperazine derivatives that significantly inhibited HAdV infection.
These six compounds showed the capacity to block HAdV and, in addition,
human cytomegalovirus (HCMV) replications at low micromolar concentration,
with little or no cytotoxicity. On the basis of our biological studies,
these molecules block HAdV and HCMV infections in different phases
of their life cycle, providing potential candidates for the development
of a new family of antiviral drugs for the treatment of infections
by DNA viruses.