Nucleoside derivatives as inhibitors of RNA-dependent RNA viral polymerase
DC CAFCFirst Claim
1. A method of treating hepatitis C virus (HCV) infection comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound of structural formula III, or a pharmaceutically acceptable salt or acyl derivatives thereof, wherein B is W is O or S;
- Y is H, C1-10 alkylcarbonyl, P3O9H4, P2O6H3, or P(O)R9R10;
R1 is CF3, or C1-4 alkyl and one of R2 and R3 is OH or C1-4 alkoxy and the other of R2 and R3 is fluoro;
R6 is H, OH, SH, NH2, C1-4 alkylamino, di(C1-4 alkyl)amino, C3-6 cycloalkylamino, halogen, C1-4 alkyl, C1-4 alkoxy, or CF3;
R5 is H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-4 alkylamino, CF3, or halogen; and
R9 and R10 are each independently hydroxy, OCH2CH2SC(═
O)t-butyl, or OCH2O(C═
O)iPr.
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Abstract
The present invention provides nucleoside derivatives which are inhibitors of RNA-dependent RNA viral polymerase. These compounds are inhibitors of RNA-dependent RNA viral replication and are useful for the treatment of RNA-dependent RNA viral infection. They are particularly useful as inhibitors of hepatitis C virus (HCV) NS5B polymerase, as inhibitors of HCV replication, and/or for the treatment of hepatitis C infection. The invention also describes pharmaceutical compositions containing such nucleoside derivatives alone or in combination with other agents active against RNA-dependent RNA viral infection, in particular HCV infection. Also disclosed are methods of inhibiting RNA-dependent RNA polymerase, inhibiting RNA-dependent RNA viral replication, and/or treating RNA-dependent RNA viral infection with the nucleoside derivatives of the present invention.
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Citations
2 Claims
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1. A method of treating hepatitis C virus (HCV) infection comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound of structural formula III, or a pharmaceutically acceptable salt or acyl derivatives thereof,
wherein B is W is O or S; -
Y is H, C1-10 alkylcarbonyl, P3O9H4, P2O6H3, or P(O)R9R10;
R1 is CF3, or C1-4 alkyl and one of R2 and R3 is OH or C1-4 alkoxy and the other of R2 and R3 is fluoro;
R6 is H, OH, SH, NH2, C1-4 alkylamino, di(C1-4 alkyl)amino, C3-6 cycloalkylamino, halogen, C1-4 alkyl, C1-4 alkoxy, or CF3;
R5 is H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-4 alkylamino, CF3, or halogen; and
R9 and R10 are each independently hydroxy, OCH2CH2SC(═
O)t-butyl, or OCH2O(C═
O)iPr. - View Dependent Claims (2)
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Specification