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Abstract The synthesis of cycloSal-FdUMP 3a-d as a new prodrug approach for FdU 1 is described. Phosphotriesters 3 release the FdUMP 2 selectively by a controlled, chemically induced tandem reaction in hydrolysis studies. The biological activity (IC50) of cycloSal-phosphotriesters 3 was evaluated in FM3A/O cells and FM3A/TK− cells.
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Abstract A paired adenosine kinase-positive/adenosine kinase-negative cell system is proposed to distinguish those adenosine analogues that need to be phosphorylated to exert their biological effects from those that are mainly targeted at S-adenosyl-L-homocysteine hydrolase.
At present, acyclovir and ganciclovir are the most frequently used antiviral drugs for the treatment of herpesvirus infections (acyclovir for herpes simplex virus and varicella-zoster virus and ganciclovir for cytomegalovirus). These compounds are amenable to both therapeutic and prophylactic use. However, the increased frequency by which drug-resistant viruses seem to emerge in immunosuppressed patients, the toxic side effects of the drugs (particularly ganciclovir), and the risk for relapses after cessation of ganciclovir therapy justify the search for additional and alternative therapeutic modalities. From this perspective various new antiviral drug candidates are reviewed, including carbocyclic analogues of ganciclovir, bromovinyldeoxyuridine derivatives, acyclic nucleoside phosphonates, and some other specific antiherpesvirus agents that have proved active against any of the herpesvirus family members (herpes simplex virus-1, herpes simplex virus-2, varicella-zoster virus, cytomegalovirus, Epstein-Barr virus, or human herpesvirus-6).