IN-VITRO AND IN-VIVO ANTIVIRAL (RNA) EVALUATION OF OROTIDINE 5'-MONOPHOSPHATE DECARBOXYLASE INHIBITORS AND ANALOGS INCLUDING 6-AZAURIDINE-5'-(ETHYL METHOXYALANINYL)PHOSPHATE (A 5'-MONOPHOSPHATE PRODRUG)
B. Gabrielsen et al., IN-VITRO AND IN-VIVO ANTIVIRAL (RNA) EVALUATION OF OROTIDINE 5'-MONOPHOSPHATE DECARBOXYLASE INHIBITORS AND ANALOGS INCLUDING 6-AZAURIDINE-5'-(ETHYL METHOXYALANINYL)PHOSPHATE (A 5'-MONOPHOSPHATE PRODRUG), Antiviral chemistry & chemotherapy, 5(4), 1994, pp. 209-220
A series of 29 pyrimidines comprising analogues of 6-azauridine (e.g.
2- and 4-thio-6-azauridine), 6-substituted uridines (including several
known inhibitors of orotidine 5'-monophosphate decarboxylase, ODCase,
e.g. pyrazofurin), and 6-azauridine-5'-(ethyl methoxyalaninyl) phosph
ate (a potential prodrug of 6-AU-5'-MP) were synthesized and evaluated
in vitro and in vivo against five RNA viruses: Japanese encephalitis
(JE), yellow fever (YF), sandfly fever (SF), Punta Toro (PT) and Venez
uelan equine encephalomyelitis (VEE) viruses. 2-Thio-6-azauridine demo
nstrated the best in vitro activity against all five viruses. However,
in vivo activity was not observed in JE-, PT- and VEE-infected mice.
The phosphate prodrug of 6-azauridine was significantly more effective
than the parent compound in the PT virus mouse model. Optimum in vivo
dose/route/schedule was determined for pyrazofurin in PT-virus-infect
ed mice.