title: Selective inhibition of Human Immunodeficiency Virus type 1 (HIV-1) by a novel family of tricyclic nucleosides.
abstract: Nucleoside 1, with an unusual tricyclic carbohydrate moiety, specifically inhibits HIV-1 replication while being inactive against HIV-2 or other (retro) viruses. In an attempt to increase the inhibitory efficacy against HIV-1, and to further explore the structural features required for anti-HIV-1 activity, different types of modifications have been carried out on this prototype compound. These include substitution of the ethoxy group at the C-4″ position by alkoxy groups of different length, branching, conformational freedom or functionalization. In addition, the 4″-ethoxy group has been removed or substituted by other functional groups. The role of the tert-butyldimethylsilyl (TBDMS) group at the 2' position has also been studied by preparing the corresponding 2'-deprotected derivative or by replacing it by other silyl (tert-hexyldimethylsilyl) or acyl (acetyl) moieties. Finally, the thymine of the prototype compound has been replaced by N-3-methylthymine, uracil or thiophenyl. Some of these compounds were endowed with a 6- to 7-fold higher selectivity than the prototype 1. The tricyclic nucleosides here described represent a novel type of selective anti HIV-1 inhibitors, targeted at the HIV-1-encoded reverse transcriptase.
authors: Instituto de Química Médica (CSIC), Juan de la Cierva 3, 28006 Madrid, Spain.
authors: María-Cruz
authors: MC
authors: Bonache
authors: Alessandra
authors: A
authors: Cordeiro
authors: Ernesto
authors: E
authors: Quesada
authors: Els
authors: E
authors: Vanstreels
authors: Dirk
authors: D
authors: Daelemans
authors: María-José
authors: MJ
authors: Camarasa
authors: Jan
authors: J
authors: Balzarini
authors: Ana
authors: A
authors: San-Félix