Antiviral nucleoside drug delivery via amino acid phosphoramidates.
Stable and water soluble amino acid phosphomonoester amidates of AZT were synthesized and shown to have potent anti-HIV-1 activity. Intracellular and cell extract metabolism studies revealed that these compounds are likely to be enzymatically converted to the corresponding monophosphates. In addition, we have shown that the half life and tissue distribution of a phosphoramidate of AZT is 5 and 10-fold greater, respectively, than AZT.
Wagner
C R
CR
Department of Medicinal Chemistry, University of Minnesota, Minneapolis 55455, USA.
Chang
S L
SL
Griesgraber
G W
GW
Song
H
H
McIntee
E J
EJ
Zimmerman
C L
CL
D000596:Amino Acids / Q000737:chemistry; D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D002460:Cell Line; D004337:Drug Carriers; D005260:Female; D006207:Half-Life; D006801:Humans; D009943:Organophosphorus Compounds / Q000008:administration & dosage* / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley
D000596:Amino Acids; D019380:Anti-HIV Agents; D004337:Drug Carriers; D009943:Organophosphorus Compounds