Influence of a Calpha-substitution on the S-pivaloyl-2-thioethyl chain on the anti-HIV activity and stability of the resulting zidovudine mononucleoside phosphotriester.
We report the synthesis, in vitro anti-HIV-1 activity and stability study of a mononucleoside phosphotriester derivative of 3'-azido-2',3'-dideoxythymidine (AZT) bearing a new biolabile phosphate-protection, namely S-pivaloyl-2-thioisopropyl (tBuSATP). This transient protection was characterized by the presence of a methyl substituent at the Calpha-position of the previously described S-pivaloyl-2-thioethyl (tBuSATE) group. Results demonstrated that the new phosphotriester entity was able to deliver selectively the corresponding 5'-mononucleotide within the infected cells. The introduction of a methyl group at the Calpha-position of the tBuSATE chain decreased the rate of this delivery.
Peyrottes
S
S
UMR 5625 CNRS-UM II, Université Montpellier II, France.
Périgau
C
C
Aubertin
A M
AM
Gosselin
G
G
Imbach
J L
JL
D004355:Drug Stability; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D013057:Spectrum Analysis; D013329:Structure-Activity Relationship; D015215:Zidovudine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*
D018894:Reverse Transcriptase Inhibitors; D015215:Zidovudine