Synthesis and biological evaluation of some cyclic phosphoramidate nucleoside derivatives.
(E)-5-(2-Bromovinyl)-2'-deoxy-5'-O-(3-methyl-2-oxo-5-formyl-1,3,2- oxazaphosphacyclopentan-2-yl)uridine has been synthesized and, under physiological conditions and without the necessity for enzyme activity, has been shown to yield the 5'-nucleotide in vitro. Unfortunately this compound is not sufficiently stable in solution for it to be tested in vivo. The biological properties of this and some related derivatives of (E)-5-(2-bromovinyl)-2'-deoxyuridine and acyclovir have been evaluated in in vitro and in vivo systems designed to show the effects of any intracellular liberation of the nucleotide. Although some of the derivatives are probably acting as prodrugs of the active nucleosides, there is no evidence for the liberation of meaningful concentrations of the 5'-nucleotide by any of the compounds.
Kumar
A
A
School of Chemistry, University of Birmingham, Great Britain.
Coe
P L
PL
Jones
A S
AS
Walker
R T
RT
Balzarini
J
J
De Clercq
E
E
D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000627:therapeutic use; D006561:Herpes Simplex / Q000188:drug therapy; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D011355:Prodrugs / Q000138:chemical synthesis* / Q000627:therapeutic use; D011817:Rabbits; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000998:Antiviral Agents; D011355:Prodrugs