Nucleoside derivatives as inhibitors of RNA-dependent RNA viral polymerase

Abstract

The present invention provides nucleoside compounds and certain derivatives thereof 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 compounds 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 compounds of the present invention.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS [0001] The present invention is related to U.S. provisional applications Ser. Nos. 60 / 263,313, filed Jan. 22, 2001; 60 / 282,069, filed Apr. 6, 2001; 60 / 299,320, filed Jun. 19, 2001; and 60 / 344,528 filed Oct. 25, 2001; the contents of each of which are hereby incorporated by reference.FIELD OF THE INVENTION [0002] The present invention provides nucleoside compounds and certain derivatives thereof 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 for the treatment of hepatitis C infection. BACKGROUND OF THE INVENTION [0003] Hepatitis C virus (HCV) infection is a major health problem that leads to chronic liver disease, such as cirrhosis and hepatocellular carcinoma, in a subs...

AI Technical Summary

Benefits of technology

"The present invention provides a method for inhibiting the replication of RNA-dependent viruses in mammals. The method involves administering a compound of structural formula I to the mammal, which inhibits the activity of the viral polymerase enzyme. The compound can be administered as a therapeutically effective amount to treat RNA-dependent viral infections in mammals. The compound has been found to specifically target the viral polymerase enzyme and has minimal effect on other viral proteins. The compound can be administered as a pharmaceutical composition or as a salt."

Problems solved by technology

Hepatitis C virus (HCV) infection is a major health problem that leads to chronic liver disease, such as cirrhosis and hepatocellular carcinoma, in a substantial number of infected individuals, estimated to be 2-15% of the world's population.

Current treatments for HCV infection, which are restricted to immunotherapy with recombinant interferon-α alone or in combination with the nucleoside analog ribavirin, are of limited clinical benefit.

Moreover, there is no established vaccine for HCV.

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