Synthesis and antiviral activity of acyclovir-5'-(phenyl methoxy alaninyl) phosphate as a possible membrane-soluble nucleotide prodrug.
We describe a synthesis of acyclovir-5'-(phenyl methoxy alaninyl) phosphate (2) from acyclovir (1). This compound was designed to act as a lipophilic, membrane-soluble prodrug of the free nucleotide. However, the biological activities of this derivative against a range of viruses indicated poor intracellular phosphate delivery, in marked contrast to the earlier successful delivery of several dideoxy anti-HIV nucleotides.
McGuigan
C
C
Welsh School of Pharmacy, Cardiff University, UK. mcguigan@cardiff.ac.uk
Slater
M J
MJ
Parry
N R
NR
Perry
A
A
Harris
S
S
D000212:Acyclovir / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D002522:Chlorocebus aethiops; D003587:Cytomegalovirus / Q000187:drug effects; D018258:Herpesvirus 2, Human / Q000187:drug effects*; D014645:Herpesvirus 3, Human / Q000187:drug effects; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D012995:Solubility; D014709:Vero Cells
D000998:Antiviral Agents; D011355:Prodrugs; C412029:acyclovir-5'-(phenyl methoxy alaninyl)phosphate; D000212:Acyclovir