Substituted purine nucleosides, phosphoroamidate and phosphorodiamidate derivatives for treatment of viral infections

摘要

This invention is directed to phosphoroamidate and phosphorodiamidate derivatives including the compounds of formula (I) having the structure;
wherein U, V, W, Z, R1, X1, X2, and Y are defined herein. These compounds and pharmaceutical compositions containing these compounds are useful in the treatment of viral infections in mammals infected by a virus in the Flaviviridae family of viruses, in particular hepatitis C virus (HCV). The compounds of this invention may be prepared by various methods known in the art of organic chemistry in general and nucleoside and nucleotide analog synthesis in particular.

主权项

1. A compound of formula (I) having the structure: whereinU and V are each independently selected from the group consisting of
H OH Cl Br I OR1 NH2 NHR2 NR2R2 SH and SR3 wherein
R1, R2, and R3 are independently C1-C6 alkyl or alkyl(C1-C3)aryl;W is independently selected from the group consisting of
I OH NH2 SH SR4 OR5 NHR6 and NR6R6, wherein
R4, R5 and R6 are independently C1-C6 alkyl or alkyl(C1-C3)aryl;X1 is OH or F;X2 is OH;Y is hydrogen or N3 (azido);Z is selected from the group consisting of
H —P(O)(OAr)NHR7 —P(O)(NHR7)2 —P(O)(O−)NHR7 —P(O)O−2 (monophosphate) and —PO2—O—PO2—O—PO3 (triphosphate) wherein
R7 is
—C(R8)(R9)C(O)OR10 wherein
R8 and R9 are independently hydrogen, alkyl, aryl(C1-C6)alkyl, or phenyl,R10 is C1-C6 alkyl aryl(C1-C6)alkyl, andAr is independently selected from the group consisting of
phenyl1-naphthyl2-naphthyl and wherein the compound has a specific formula selected from the group consisting of the following:and the pharmaceutically acceptable salts thereof.