Open AccessInfluence of a Cα-Substitution on the S-Pivaloyl-2-Thioethyl Chain on the Anti-HIV Activity and Stability of the Resulting Zidovudine Mononucleoside Phosphotriester
Author(s) -
Suzanne Peyrottes,
Christian Philouze,
A.M. Aubertin,
Gilles Gosselin,
J.L. Imbach
Publication year - 2001
Publication title -
antiviral chemistry and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.919
H-Index - 51
eISSN - 2040-2066
pISSN - 0956-3202
DOI - 10.1177/095632020101200403
Subject(s) - substituent , prodrug , stereochemistry , zidovudine , chemistry , amidine , human immunodeficiency virus (hiv) , methyl group , in vitro , biochemistry , biology , virology , group (periodic table) , organic chemistry , viral disease
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.