An Isomer of Galidesivir That Potently Inhibits Influenza Viruses and Members of the Bunyavirales Order.

We report for the first time the antiviral activities of two (antiviral imino--nucleosides) and , structurally related to galidesivir (Immucillin A, BCX4430). An containing the 4-aminopyrrolo[2,1-][1,2,4-triazine] nucleobase found in remdesivir exhibited submicromolar inhibition of multiple strains of influenza A and B viruses, as well as members of the order. We also report the first syntheses of ProTide prodrugs of monophosphates, which unexpectedly displayed poorer viral inhibition than their parent nucleosides . An efficient synthesis of the 4-aminopyrrolo[2,1-][1,2,4-triazine]-containing was developed to enable preliminary studies, wherein it displayed significant toxicity in BALB/c mice and limited protection against influenza. Further modification of this anti-influenza will therefore be required to improve its therapeutic value.