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

S Peyrottes; C Périgau; A M Aubertin; G Gosselin; J L Imbach

doi:10.1177/095632020101200403

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

Antivir Chem Chemother. 2001 Jul;12(4):223-32. doi: 10.1177/095632020101200403.

Authors

S Peyrottes¹, C Périgau, A M Aubertin, G Gosselin, J L Imbach

Affiliation

¹ UMR 5625 CNRS-UM II, Université Montpellier II, France.

PMID: 11771731
DOI: 10.1177/095632020101200403

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Drug Stability
Reverse Transcriptase Inhibitors / chemistry*
Reverse Transcriptase Inhibitors / pharmacology*
Spectrum Analysis
Structure-Activity Relationship
Zidovudine / analogs & derivatives*
Zidovudine / chemistry
Zidovudine / pharmacology*

Substances

Reverse Transcriptase Inhibitors
Zidovudine