Effects of aryl substituents on the anti-HIV activity of the arylphosphoramidate derivatives of stavudine.
We compared the anti-HIV activity of 13 phenyl phosphate derivatives of stavudine (2',3'-didehydro-2',3'-dideoxythymidine/d4T) by examining their ability to inhibit HIV-1 replication in human peripheral blood mononuclear cells. Our results show that the introduction of electron-withdrawing substituents enhances the activity of these phosphoramidate derivatives. The rate of chemical hydrolysis under alkaline conditions (but not the lipophilicity) predicted the potency of the compounds.
Uckun
Fatih M
FM
Department of Virology, Parker Hughes Institute, St. Paul, Minn., USA. fatih_uckun@ih.org
Samuel
P
P
Qazi
S
S
Chen
C
C
Pendergrass
S
S
Venkatachalam
T K
TK
D019380:Anti-HIV Agents / Q000737:chemistry* / Q000494:pharmacology*; D002478:Cells, Cultured; D006678:HIV / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis / Q000187:drug effects; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000821:virology; D015394:Molecular Structure; D018119:Stavudine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects
D019380:Anti-HIV Agents; D018119:Stavudine