STUDIES OF THE PHARMACOKINETICS AND TOXICOLOGY OF 2',3'-DIDEOXY-BETA-L-5-FLUOROCYTIDINE (BETA-L-FDDC) AND 2',3'-DIDEOXY-BETA-L-CYTIDINE (BETA-L-DDC) IN-VIVO AND SYNTHESIS AND ANTIVIRAL EVALUATIONS OF 2',3'-DIDEOXY-BETA-L-5-AZACYTIDINE

The pharmacokinetics and toxicology of 2',3'-dideoxy-beta-L-5-fluorocy tidine (beta-L-FddC) and 2',3'-dideoxy-beta-L-cytidine (beta-L-ddC) in mice was investigated. In addition, 2',3'-dideoxy-beta-L-5-azacytidin e (beta-L-5-aza-ddC) and its alpha-L-anomer (alpha-L-5-aza-ddC) were s ynthesized by coupling the silylated 5-azacytosine derivative with rt- butyldimethyisilyl)-2,3-dideoxy-L-ribofuranose, followed by separation of the alpha- and beta-anomers and were evaluated in vitro against HB V and HIV. beta-L-5-aza-ddC was found to show significant anti-HBV act ivity at approximately the same level as 2',3'-dideoxy-beta-D-cytidine (ddC), which is a known anti-HBV agent. beta-L-5-aza-ddC was not cyto toxic to L1210, P388, S-180, and CCRF-CEM cells up to a concentration of 100 mu M. Conversely, the alpha-L-anomer was not active against HBV at the same concentration.