Zidampidine, an aryl phosphate derivative of AZT: in vivo pharmacokinetics, metabolism, toxicity, and anti-viral efficacy against hemorrhagic fever caused by Lassa virus

Developments in Antiviral Drug Design, Discovery and Development in 2004

“…Studies in mice demonstrated that vaginal infection by HSV-1 and HSV-2 can be blocked by preincubation of the viruses with a soluble recombinant form of nectin-1 [885,886]. The utility of the over-the-counter topical HSV fusion inhibitor docosanol (336) has been summarized [887] and a survey of inhibitors of HSV entry is included in the review by Firestine [888].…”

“…An aryl phosphoramidate derivative, zidampidine (94), liberates Ala-zidovudine-monophosphate and zidovudine (6) following IV administration to mice and protects against hemorrhagic fever induced by inoculation with Lassa virus when administered IP at non-toxic doses [336]. In vitro metabolic studies with a tritiated form of the 5'-hydrogenphosphate derivative 95, a zidovudine prodrug with lower toxicity than the parent molecule, indicated that the accumulation of metabolites in cells was slower than for zidovudine and that the major species in cells was zidovudine monophosphate [337].…”

“…The synthesis and characterization of several prodrugs of the monophosphate of zidovudine (6) have been described [335][336][337]. An aryl phosphoramidate derivative, zidampidine (94), liberates Ala-zidovudine-monophosphate and zidovudine (6) following IV administration to mice and protects against hemorrhagic fever induced by inoculation with Lassa virus when administered IP at non-toxic doses [336].…”

Viral Hemorrhagic Fevers: Current Status of Endemic Disease and Strategies for Control

“…This consists of 2 g orally in four divided doses for 7 days [14,16,17,78,84,95]. Zidampidine, a derivative of zidovudine, is a new agent that seems effective in treating the CD-1 mouse model of Lassa VHF [96].…”

The purification and characterization of deoxycytidine kinase from calf thymus

“…Thus some emphasis has been placed on developing a commercial and simple way of synthesizing the monophosphate derivative of the nucleoside analog (Uckum et al 2005;Kitade 1997). However, no reference or protocol had been reported that related to the enzymatic synthesis of the nucleoside analog derivatives.…”