Antiviral methods employing double esters of 2′, 3′-dideoxy-3′-fluoroguanosine
A method for treatment of HBV and HIV infections comprising administering the compound or salt of formula Ig
1. A synthetic intermediate with the formula IId:
where PG-R 2 is the acyl residue of an aliphatic L-amino acid, which is optionally N-protected, p is 0-5, q is 0-5 and X is hydroxy or an activating group.
2. An intermediate according to claim 1 , wherein X is halo.
3. An intermediate according to claim 1 , wherein p is 0.
4. An intermediate according to claim 1 , wherein q is 0.
5. An intermediate according to claim 4 , wherein the compound has the stereochemistry of L lactic acid.
6. An intermediate according to claim 5 wherein R 2 is N-protected valyl or N-protected isoleucyl.
7. An intermediate according to claim 6 selected from the group consisting of:
2(-L valyloxy)propanoic acid, 2-(N-Boc-L-valyloxy)propanoic acid, 2-(N-Fmoc-L-valyloxy)propanoic acid, 2-(N-CBZ-L-valyloxy)propanoic acid, and the acid halides thereof.
8. A process for the preparation of 2′,3′-dideoxy-3′-fluoro-5′-O-[2-(-L-valyloxy)-propionyl]guanosine comprising the esterification of 2′-3′-dideoxy-3′-fluoroguanosine with an intermediate selected from the group consisting of 2(-L-valyloxy)propanoic acid, 2-(N-Boc-L-valyloxy)propanoic acid, 2-(N-Fmoc-L-valyloxy)propanoic acid, 2-(N-CBZ-L-valyloxy)propanoic acid, and the acid halides thereof, followed by removal of the Fmoc, Boc or CBZ N-protecting group.