Some embodiments of the present invention include nucleoside 5-monophosphate derivative compounds, their preparation and their uses. In some embodiments, such compounds are useful to treat hepatitis C viral infections.

The present invention relates to compounds of the formula I:

##STR00001##

including any possible stereoisomers thereof, wherein R.sup.9 has the meaning as defined herein,or a pharmaceutically acceptable salt or solvate thereof.

The present invention also relates to processes for preparing said compounds, pharmaceutical compositions containing them and their use, alone or in combination with other HCV inhibitors, in HCV therapy.

The invention provides compounds of the formula:

##STR00001##

wherein B is a nucleobase selected from the groups (a) to (d):

##STR00002##

and the other variables are as defined in the claims,
which are of use in the treatment or prophylaxis of hepatitis C virus infection, and related aspects.

Gemcitabine analogs, including monophosphorylated analogs, are described herein and are suitable for use in pharmaceutical compositions, kits and treatment methods. The treatment methods include treatment of viral infections, including, but not limited to, treatment of Hepatitis C Virus, and uncontrolled cellular proliferation, including cancer, such as, but not limited to, non-small cell lung cancer, pancreatic cancer, bladder cancer, breast cancer, liver cancer, esophageal cancer and lymphoma.

To provide a chiral reagent or a salt thereof. The chiral reagent has following chemical formula (I). In the formula (I), G.sup.1 and G.sup.2 are independently a hydrogen atom, a nitro group (NO.sub.2), a halogen atom, a cyano group (CN), a group of formula (II) or (III), or both G.sup.1 and G.sup.2 taken together to form a group of formula (IV). ##STR00001##

To provide a chiral reagent or a salt thereof. The chiral reagent has following chemical formula (I). In the formula (I), G.sup.1 and G.sup.2 are independently a hydrogen atom, a nitro group (NO.sub.2), a halogen atom, a cyano group (CN), a group of formula (II) or (III), or both G.sup.1 and G.sup.2 taken together to form a group of formula (IV). ##STR00001##

Methods, Compositions, and Systems are provided for nucleic acid sequencing where the sequential incorporation of nucleotides uses two distinct chemical steps. A plurality of nucleotide analogs, each having a labeled leaving group at its 3 hydroxyl can be sequentially added to a growing strand in the presence of a selective cleaving activity that cleaves the 3 hydroxyl leaving group preferentially after it has been incorporated. The selective cleaving agent can comprise an exonuclease activity, and the exonuclease activity can be a polymerase-associated exonuclease activity. Nucleotide analogs having labels on both a cleavable polyphosphate portion and on a 3 hydroxyl leaving group can provide signals characteristic of nucleotide analog incorporation. Systems having illumination optics, collection optics, and substrates observe signals from the labels as they are being incorporated into a growing nucleic acid strand, allowing for the sequencing of template nucleic acids.

Methods, Compositions, and Systems are provided for nucleic acid sequencing where the sequential incorporation of nucleotides uses two distinct chemical steps. A plurality of nucleotide analogs, each having a labeled leaving group at its 3 hydroxyl can be sequentially added to a growing strand in the presence of a selective cleaving activity that cleaves the 3 hydroxyl leaving group preferentially after it has been incorporated. The selective cleaving agent can comprise an exonuclease activity, and the exonuclease activity can be a polymerase-associated exonuclease activity. Nucleotide analogs having labels on both a cleavable polyphosphate portion and on a 3 hydroxyl leaving group can provide signals characteristic of nucleotide analog incorporation. Systems having illumination optics, collection optics, and substrates observe signals from the labels as they are being incorporated into a growing nucleic acid strand, allowing for the sequencing of template nucleic acids.

Disclosed are P-stereogenic groups that may be used in the synthesis of compounds including stereochemically enriched P-stereogenic phosphorothioates. P-stereogenic groups may be provided in nucleoside phosphoramidites including a sugar bonded to a nucleobase and to a stereochemically enriched phosphoramidite as well as methods of their use and methods of making them.

Disclosed are P-stereogenic groups that may be used in the synthesis of compounds including stereochemically enriched P-stereogenic phosphorothioates. P-stereogenic groups may be provided in nucleoside phosphoramidites including a sugar bonded to a nucleobase and to a stereochemically enriched phosphoramidite as well as methods of their use and methods of making them.