The pyridine system derivatives have been studied as antiviral drug new models against HIV infection using bioisosterism as a powerful tool. In the last decades, the number of this work, thienopyridine derivatives were evaluated as an HSV-1 inhibitor to since the elevated number of acyclovir resistance in immunocompromised patients could promote a continuous viral pool increase and disease recurrence. In these substances, thienopyridine derivative with radical nitrate in para position (109) was able to inhibit 99% of HSV-1 replication in Vero cells with EC 50 value of 100 pM, and SI value three times higher than acyclovir. In kinetic enzymatic assay this substance was also able to inhibit about 50% of HSV-1 DNA polymerase but in a non-competitive mechanism a new synergic system to control herpes infections. Preliminary in vivo model studies revealed that substance 109 is toxic when administered in 300 g/mL concentrations. In this work, we concluded that thienopyridine derivatives can be considered a promising new anti-HSV-1 drug and can be used for clinical testing.
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