80384-36-7

The invention relates to the use of an uridine derivative of formula (I): wherein R1 represents monohalogenated alkynyl or dihalogenated alkenyl;R2 is chosen from among hydrogen, hydroxyl, -O-alkyl, -O-CO-alkyl and halogen;R3 is chosen from among hydrogen, hydroxyl, -O-alkyl, -O-CO-alkyl, halogen, -SH, -S-alkyl and N3; andR4 is chosen from among hydroxyl, -O-alkyl, -O-CO-alkyl, -O-phosphate, -O-diphosphate, -O-triphosphate and -O-phosphonate, as well as its possible tautomers, its possible pharmaceutically acceptable addition salts with an acid or a base, and its N-oxide forms, for the preparation of a drug having antiviral activity against a Flaviviridae.

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).

5-Bromoethynyluracil and its deoxyriboside can be prepared in good yields starting from dibromovinyluracil, which is accesible by literature methods. 5-Bromoethynyl-deoxyuridine is less effective against HSV-1 than E- (bromovinyl)-deoxyuridine but, similar to BVDU, seems to exhibit a certain selectivity toward HSV-1. Molecular calculations prove the spatial similarity of both compounds.