The present disclosure relates to compounds, compositions and methods for the treatment of hepatitis C virus (HCV) infection. Also disclosed are pharmaceutical compositions containing such compounds and methods for using these compounds in the treatment of HCV infection.

Hepatitis C virus inhibitors

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.

Nucleoside derivatives as inhibitors of rna-dependent rna viral polymerase

An enantiomer, diastereoisomer or tautomer of a compound, represented by formula I: wherein A, B, R1, R2, R3, R4, R5, R6, R7, R8, R9, and R10 are as defined herein, or a salt or ester thereof, as an inhibitor of HCV NS5B polymerase.

Viral Polymerase Inhibitors

Compounds of formula ##STR1## are HIV protease inhibitors. These compounds are useful in the prevention or treatment of infection by HIV and in the treatment of AIDS, either as compounds, pharmaceutically acceptable salts, pharmaceutical composition ingredients, whether or not in combination with other antivirals, immunomodulators, antibiotics or vaccines. Methods of treating AIDS and methods of preventing or treating infection by HIV are also described.

Hiv protease inhibitors useful for the treatment of aids

A method and composition for treating a host infected with hepatitis C comprising administering an effective hepatitis C treatment amount of a described 1′, 2′ or 3′-modified nucleoside or a pharmaceutically acceptable salt or prodrug thereof, is provided.

Methods and compositions for treating hepatitis C virus

Use of compounds of formula (I), wherein R1 is hydrogen, hydroxy, alkyl, hydroxyalkyl, alkoxy, halogen, cyano, isocyano or azido; R2 is hydrogen, hydroxy, alkoxy, chlorine, bromine or iodine; R3 is hydrogen; or R?2 and R3? together represent =CH?2?; or R?2 and R3? represent fluorine; X is O, s or CH?2?; a, b, c, d denoting asymmetric carbon atoms each of which is substituted with 4 different substituents; and B signifies a purine base B1 which is connected through the 9-nitrogen of formula (B1), wherein R?4? is hydrogen, hydroxyl, alkyl, alkoxy, alkylthio, aryloxy, arylthio, heterocyclyl, NR7R8, halogen or SH; R5 is hydrogen, hydroxy, alkyl, haloalkyl, cycloalkyl, alkoxy, alkylthio, aryl, aryloxy, arylthio, heterocyclyl, heterocyclylamino, halogen, NR?7R8, NHOR9, NHNR7R8? or SH; R6 is hydrogen, hydroxy, alkyl, alkoxy, alkylthio, aryloxy, arylthio, heterocyclyl, NR7R8, halogen, SH or cyano; R?7 and R8? are independently of each other hydrogen, alkyl, aryl, hydroxyalkyl, alkenylalkyl, alkynylalkyl, cycloalkyl or acyl; R9 is hydrogen, alkyl or aryl; or B signifies an oxidised purine base B2 which is connected through the 9-nitrogen of formula (B2), wherein R?4, R5 and R6? are as defined above; or B signifies a purine base B3 which is connected through the 9-nitrogen of formula (B3), wherein R?4 and R6? are as defined above; R10 is hydrogen, alkyl or aryl; Y is O, S or NR11; R11 is hydrogen, hydroxy, alkyl, OR9, heterocyclyl or NR?7R8; R7, R8 and R9? are as defined above; or B signifies a pyrimidine base B4 which is connected through the 1-nitrogen of formula (B4), wherein Z is O or S; R12 is hydrogen, hydroxy, alkyl, alkoxy, haloalkyl, alkylthio, aryl, aryloxy, arylthio, heterocyclyl, heterocyclylamino, halogen, NR?7R8, NHOR9, NHNR7R8? or SH; R13 is hydrogen, alkyl, hydroxyalkyl, alkoxyalkyl, haloalkyl, cycloalkyl or halogen; R?7, R8 and R9? are as defined above; or B signifies a pyrimidine base B5 which is connected through the 1-nitrogen of formula (B5), wherein Y, Z, R10 are as defined above for the treatment of diseases mediated by the Hepatitis C Virus (HIV) or for the preparation of a medicament for such treatment. The invention is concerned with novel and known purine and pyrimidine nucleoside derivatives, their use as inhibitors of subgenomic Hepatitis C Virus (HCV) RNA replication and pharmaceutical compositions of such compounds.

Nucleoside derivatives for the treatment of hepatitis c

The present invention relates to nucleoside derivatives for the treatment of Hepatitis C viral infections including compounds of formula I (I), to pharmaceutical compositions comprising these compounds and methods for treatment or prophylaxis of Hepatitis C Virus mediated diseases employing said compounds in monotherapy or in combination therapy. The present invention further provides a process for preparing 1',3',4'-triacyl pyrimidine nucleoside from a N,1',3',4'-tetraacylpyrimidine nucleoside.

Antiviral nucleoside derivatives

The present invention relates to the use of nucleoside derivatives of Formula (I) wherein B signifies a 9-purinyl residue B1 of Formula (B1) or a 1-pyrimidyl residue B2 of Formula (B2) wherein the symbols are as defined in the specification, and of pharmaceutically acceptable salts thereof; for the treatment of diseases mediated by the Hepatitis C Virus (HCV), for the preparation of a medicament for such treatment and to pharmaceutical compositions containing such compounds.

4'-substituted nucleosides for the treatment of diseases mediated by the hepatitis C virus

Verbindungen der allgemeinen Formel Compounds of general formula worin AC 1-8 -Alkylen, R 1 Halogen, C 1-4 -Alkyl oder Halo-(C 1-4 -alkyl), R 2 Wasserstoff, Hydroxy oder Acyloxy, R 3 Wasserstoff oder C 1-4 -Alkyl, R 4 Aryl oder Aryloxy und X Sauerstoff oder NH bedeutet, und Tautomere davon haben antivirale Eigenschaften. wherein A is C 1-8 alkylene, R 1 is halogen, C 1-4 alkyl or halo (C 1-4 alkyl), R 2 is hydrogen, hydroxy or acyloxy, R 3 is hydrogen or C 1-4 alkyl, R 4 is aryl or aryloxy and X is oxygen or NH, and tautomers thereof have antiviral properties. Sie werden in an sich bekannter Weise hergestellt. They are produced in a conventional manner.

Pyrimidine derivatives, their preparation and medicaments containing these derivatives

The present invention relates to the hemisulfate salt of 4-amino-1-((2r,3r,4s,5r)-5-azido-3,4-dihydroxy-5-hydroxymethyl-tetrahydro-furan-2-yl)-1h-pyrimidin-2-one with improved stability and physical properties which facilitate manufacturing, handling and formulating I and polymorphic crystalline forms thereof.

Martin Joseph Armstrong

Papers

Nucleoside derivatives for the treatment of hepatitis c

Antiviral nucleoside derivatives

4'-substituted nucleosides for the treatment of diseases mediated by the hepatitis C virus

Pyrimidine derivatives, their preparation and medicaments containing these derivatives

An hydrous crystalline 4-amino-1-((2r,3r,4s,5r)-5-azido-3,4-dihydroxy-5-hydroxymethyl-tetrahydro-furan-2-yl)-1h-pyrimidin-2-one