Nucleoside derivatives as inhibitors of RNA-dependent RNA viral polymerase
DC CAFC
First 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.
176 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
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- Resources
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Current AssigneeISIS Pharmaceuticals Incorporated, Merck Sharp & Dohme LLC (Merck & Co., Inc.)
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Original AssigneeISIS Pharmaceuticals Incorporated, Merck & Co., Inc.
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InventorsBhat, Balkrishen, MacCoss, Malcolm, Olsen, David B., Prakash, Thazha P., Cook, Phillip Dan, Eldrup, Anne B., Carroll, Steven S.
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Primary Examiner(s)Price, Elvis O.
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Assistant Examiner(s)Henry, Michael C.
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Application NumberUS10/250,873Publication NumberTime in Patent Office1,698 DaysField of Search514/49, 514/43, 514/45, 514/42, 514/50, 514/52, 514/46, 536/28.4, 536/28.5, 536/26.12, 536/26.13US Class Current514/49CPC Class CodesA61K 2300/00 Mixtures or combinations of...A61K 31/7056 containing five-membered ri...A61K 31/7064 containing condensed or non...A61K 31/7068 having oxo groups directly ...A61K 31/7076 containing purines, e.g. ad...A61K 38/212 IFN-alphaA61K 38/2292 Thymosin; Related peptidesA61K 45/06 Mixtures of active ingredie...A61K 9/4858 Organic compoundsC07H 19/10 with the saccharide radical...C07H 19/14 Pyrrolo-pyrimidine radicalsC07H 19/20 with the saccharide radical...Y02P 20/582 Recycling of unreacted star...
