Purine 2'-deoxy-2'-fluororibosides as antiinfluenza virus agents

Twenty purine 2'-deoxy-2'-fluororibosides were synthesized by enzymic pentosyl transfer from 2'-deoxy-2'-fluorouridine. Each nucleoside analogue was assayed for cytotoxicity in uninfected Madin-Darby canine kidney cells and for their ability to suppress influenza A virus infections in these cells. The most potent antivirial activity was observed with analogues having an amino group in the 2-position of the purine moiety. All 2-unsubstituted analogues were less potent than their 2-amino counterparts. Furthermore, 2-methyl,2-methoxy, or 2-fluoro substitution obliterated antivirial activity. The most cytotoxic member of the series was the 2-fluoro-6-amino analogue (IC50 = 120 microM). 2'-Deoxy-2'-fluoroguanosine and those congeners readily converted to it by adenosine deaminase showed the most potent antivirial activity (IC50 = 15-23 microM). Little cytotoxicity was observed with this subgroup of analogues which renders them worthy of further investigation as potential antiinfluenza agents.