6-SUBSTITUTED DERIVATIVES OF CARBOVIR - ANTI-HIV ACTIVITY

A series of 6-alkoxy and 6-alkylamino carbovir derivatives were synthe sized in order to evaluate prodrug approaches to increased bioavailabi lity of the anti-HIV agent, carbovir. All of the compounds were active against HIV with the N-alkyl derivatives less active than the corresp onding O-alkyl derivatives. The adenosine deaminase inhibitor, EHNA, h ad no effect on the anti-HIV activity of 6-propoxycarbovir, while the adenylic acid deaminase inhibitor, 2'-deoxycoformycin, significantly d ecreased antiviral activity. These observations suggest that the 6-alk oxycarbovirs are metabolized directly to the monophosphates and are su bsequently converted to carbovir monophosphate via adenylic acid deami nase.