Modified benzimidazole nucleosides as antiviral agents

C - Chemistry – Metallurgy – 07 – H

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C07H 19/052 (2006.01) A61K 31/70 (2006.01) C07D 471/04 (2006.01) C07H 7/06 (2006.01) C07H 11/00 (2006.01)

Patent

CA 2244378

This invention pertains to nucleoside analogs which have antiviral activity and improved metabolic stability. More specifically, this invention pertains to modified sugar benzimidazole nucleosides, as exemplified by compounds such as benximidazole nucleosides posessing a fluorinated sugar-like moiety (for example, a 2'-fluoro-furanosyl moiety or a 3'-fluoro- furanosyl moiety), and may be represented by formula (I) wherein R1 is a fluorinated sugar-like moiety; and R2, R4, R5, R6 and R7 are benzimidazole substituents, such as -H, halogens (e.g., -F, -Cl, -Br, -I), -NO2, -NR2 (where R is independently -H or an alkyl group having 1-6 carbon atoms), -OR (where R is -H or an alkyl group having 1-6 carbon atoms), -SR (where R is -H or a hydrocarbyl of 1-10 carbon atoms), and -CF3. In one embodiment R1 is 2'-fluoro-furanosyl or 3'-fluoro-furanosyl; R2 is -H, -F, -Cl, -Br, -I, or-NR2, wherein R is independently -H or an alkyl group having 1-6 carbon atoms; R4, R5, R6 and R7 are independently -H, -F, -Cl, -Br, or -I.

L'invention concerne des analogues de nucléosides ayant une activité antivirale et une stabilité métabolique améliorée. Plus spécifiquement, elle concerne des nucléosides de benzimidazole à sucres modifiés, tels que des nucléosides de benzimidazole possédant une fraction de type sucre fluoré (par exemple, une fraction 2'-fluoro-furanosyle ou une fraction 3'-fluoro-furanosyle), qui peuvent être représentés par la formule suivante (I), où R<1> est une fraction de type sucre fluoré; et R<2>, R<3>, R<4> et R<5> sont des substituants benzimidazole, tels que -H, halogènes (par exemple F, Cl, Br, I), NO2, NR2 (où R est indépendamment -H ou un groupe alkyle contenant 1 à 6 atomes de carbone), -OR (où R est -H ou un groupe alkyle contenant 1 à 6 atomes de carbone), SR (où R est -H ou hydrocarbyle contenant 1 à 10 atomes de carbone) et -CF3. Dans un mode de réalisation, R<1> est 2'-fluoro-furanosyle ou 3'-fluoro-furanosyle; R<2> est -H, -F, -Cl, -Br, -I ou -NR2, où R est indépendamment -H ou un groupe alkyle contenant 1 à 6 atomes de carbone; R<4>, R<5>, R<6> et R<7> sont indépendamment -H, -F, -Cl, -Br ou -I.

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