Proximal fleximer analogues of 2'-deoxy-2'-fluoro-2'-methyl purine nucleos(t)ides: Synthesis and preliminary pharmacokinetic and antiviral evaluation.

In this study, proximal fleximer nucleos(t)ide analogues of Bemnifosbuvir were synthesized and evaluated for their potential to serve as antiviral therapeutics. The final parent flex-nucleoside and ProTide modified flex-nucleoside analogues were tested against several viral families including flaviviruses, filoviruses, and coronaviruses. Modest activity against Zaire Ebola virus was observed at 30 μM for compound ProTide modified analogue. Neither compound exhibited activity for any of the other viruses tested. The parent flex-nucleoside analogue was screened for toxicity in CD-1 mice and showed no adverse effects up to 300 mg/kg, the maximum concentration tested.