Submission Details

Design Rationale:

The suggested drugs are relatively simple modifications of an already known drug, further described in the notes. Fragments were chosen by visually screening where the piperazine motif seemed most fitting. The first variants are halogen substitutions. The use of fluorine in the 6 position is likely to increase solubility of the drug, and I suspect that substitution with more pharmacologically interesting halogens will retain this property. The other designs are more focused on its role as a pyrimidine analogue following phosphorylation in-vivo. Substituents in the 5 position increase steric hindrance of this molecule and may lead to greater dysfunction of viral RNA incorporating these compounds. Changes to the amide moiety will affect the ability of this molecule to engage in hydrogen bonding with other nitrogenous bases, again affecting the functionality of this molecule as a component of viral RNA. There are far too many possible changes here to list and so the example given was picked to represent this and not for the properties of that particular configuration.

Other Notes:

The following compounds are modifications of the the antiviral 'Favipiravir', a pyrazine-based compound with exceptional albeit not entirely understood efficacy against various RNA viruses. Favipiravir has already demonstrated in-vivo efficacy against SARS-CoV-2 in preliminary trials. I consider variations of this compound to be particularly attractive targets as it is both simple to synthesize (https://doi.org/10.1007/s11696-018-0654-9) and essentially nontoxic (https://doi.org/10.1016%2Fj.antiviral.2009.02.198).

Inspired By: