Synthesis and anti-HIV evaluation of new 2',3'-dideoxy-3'-thiacytidine prodrugs

Article abstract of DOI:10.1080/15257770008035031

A series of anti-HIV prodrugs possessing various polyaminated side arms have been developed. The incorporation of a N-Boc protected monoamine or diamine side arm into the backbone of the 2',3'-dideoxy-3'-thiacytidine 1 (BCH-189) provided an increase in antiviral potency, which could be several orders magnitude greater than the parent drug (1) depending on the cell culture systems used (MT-4 or MDMs). Twenty six 2',3'-dideoxy-3'-thiacytidine prodrugs which differ from each other by the length, the nature of the 5'-O function and the 5'-O or/and N-4 position on the nucleoside moiety were synthesized. Among this new series of prodrugs, several congeners (12c and 12a) were found to inhibit HIV-1 replication in cell culture with 50% effective concentrations EC₅₀ of 10 and 50 nM respectively, in MT-4 cells. Compound 12c was found more active on infected MDMs cells with 50% effective concentration of 0.01 nM. The synthesis and the antiviral properties of these compounds are discussed.

Full text of DOI:10.1080/15257770008035031

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Synthesis and anti-HIV evaluation of new
2′,3′- dideoxy-3′-thiacytidine prodrugs
Nicolas Mourier a b , Michel Camplo a b , Giovanna Schioppacassi
Della Bruna c , Francesco Pellacini c , Domenico Ungheri c , Jean-
Claude Chermann b & Jean-Louis Kraus a b
a Laboratoire de Chimie Biomoléculaire, Faculté des Sciences de
Luminy , Case 901 12288, Marseille Cedex, 9, France Phone: (33) 491
82 91 41 Fax: (33) 491 82 91 41 E-mail:
b Unité INSERM U 322, Rétrovirus et Maladies Associées, Campus
Universitaire de Luminy , BP 33, 12273, Marseille Cedex, 9, France
c Zambon Research , Via Lillo del Duca, 10, 20091, Bresso-Milano,
Italy
Published online: 05 Nov 2010.
To cite this article: Nicolas Mourier , Michel Camplo , Giovanna Schioppacassi Della Bruna , Francesco
Pellacini , Domenico Ungheri , Jean-Claude Chermann & Jean-Louis Kraus (2000) Synthesis and anti-
HIV evaluation of new 2′,3′- dideoxy-3′-thiacytidine prodrugs, Nucleosides, Nucleotides and Nucleic
Acids, 19:7, 1057-1091, DOI: 10.1080/15257770008035031
To link to this article: http://dx.doi.org/10.1080/15257770008035031
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