Ab initio studies of the antiviral drug 1-(2-fluoro-2-deoxy-beta-D-arabinofuranosyl) thymine.
The antiviral drug 1-(2-fluoro-2-deoxy-beta-D-arabinofuranosyl) thymine (FMAU) exhibits a high therapeutic index against a number of herpesviruses. As with other drugs which are nucleoside analogs, such as 1-(2-fluoro-2-deoxy-beta-D-arabinofuranosyl)-5-iodocytosine and others, the activity seems to be strongly related to the presence of a fluorine atom in the sugar moiety, in the arabino position. Theoretical calculations, using quantum-chemical methods, are used to elucidate the role of the fluorine in the arabino position and to provide information about the sugar puckering. The results seem to indicate that the fluorine atom prevents the rotation of the base around the sugar-base bond, locking it into an anti structure (Fig. 2,A3) which might be related to its exposure to enzymatic attack. The sugar study confirms the endo position (above the plane) of the C'2 carbon as opposed to the endo position of the C'3 carbon.
D000998:Antiviral Agents / Q000494:pharmacology*; D001086:Arabinofuranosyluracil / Q000031:analogs & derivatives* / Q000494:pharmacology; D006564:Herpesviridae / Q000187:drug effects; D008968:Molecular Conformation; D013329:Structure-Activity Relationship; D014529:Uridine / Q000031:analogs & derivatives*
D000998:Antiviral Agents; D001086:Arabinofuranosyluracil; C034935:clevudine; D014529:Uridine