Influence of a Cα-Substitution on the S-Pivaloyl-2-Thioethyl Chain on the Anti-HIV Activity and Stability of the Resulting Zidovudine Mononucleoside Phosphotriester
Free accessResearch articleFirst published online August, 2001
Influence of a Cα-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 Cα-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 Cα-position of the tBuSATE chain decreased the rate of this delivery.
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