Substituted Purine Nucleosides, Phosphoramidate and Phosphordiamidate Derivatives for Treatment if Viral Infections

摘要

This invention is directed to compounds of Formula (I) having the structure that are useful in the treatment of viral infections in mammals, particularly in humans, mediated, at least in part, by a virus in the Flaviviridae family of viruses.;

主权项

1. A compound of formula (I) having the structure: wherein U and V are each independently selected from the group consisting of
hydrogenOHClBrIOR1NH2NHR2NR2R3SH
andSR4; Wherein R1, R2, R3, and R4 are independently C1-C6 alkyl or aryl(C1-C3)alkyl; or R2 and R3, together with the nitrogen atom to which they are attached, may join to form a 4-6 membered ring; X1 is H or F; X2 is F or H, with the requirement that X1≠X2; X3 is CH3 or C1-C6 alkyl; Z is selected from the group consisting of
hydrogen—P(O)(OAr)NHR5—P(O)(NHR5)2—P(O)(NHR5)(NHR6)—P(O)(OH)NHR6—P(O)(OH)2 (monophosphate)
and—P(O)(OH)—O—P(O)(OH)—O—P(O)(OH)2 (triphosphate); wherein
R5 and R6 are independently
—C(R7)(R8)C(O)OR9;wherein
R7 and R8 are independently hydrogen, alkyl, aryl(C1-C6)alkyl, or phenyl;R9 is independently C1-C6 alkyl,aryl(C1-6)alkyl,or(4-pyranyl);and Ar is independently selected from the group consisting of
phenyl1-naphthyl2-naphthyl and tautormers and pharmaceutically acceptable salts thereof.