Synthesis of 5-haloethynyl- and 5-(1,2-dihalo)vinyluracil nucleosides: Antiviral activity and cellular toxicity

In this article, we report the synthesis of hitherto unknown 5-haloethynyl and 5-(1,2-dihalo)vinyluracil nucleosides in the 2′-deoxy, 3′-deoxy- and ribosyl series, and we discuss their in vitro anti-HIV and anti-HCV activities and cellular toxicitites. As a result, on the basis of their selectivity index (SI) obtained with the HCV replicon system, but also on their cytotoxicity on peripheral blood mononuclear, CEM and VERO cell lines, the best compounds were the 5-bromoethynyluridine (SI = 3.2) and the 5-(1-chloro-2-iodo)vinyluridine (SI > 2.8).

The synthesis and evaluation of eighteen, hitherto unknown, 5-haloethynyl-and 5-(1,2-dihalo)vinyluracil-(2′-deoxy-, ribo-, and 3′-deoxy)-nucleosides and their in vitro antiviral activity (HCV, HIV, BVDV) and toxicity are described.Figure optionsDownload as PowerPoint slide