The present disclosure provides procedures and intermediates for the preparation of Sofosbuvir, comprising the step of reacting a compound of formula 2: wherein R.sub.1 and R.sub.2 can independently be hydrogen or halogen, provided that at least one of R.sub.1 and R.sub.2 is a halogen. ##STR00001##

The present disclosure provides procedures and intermediates for the preparation of Sofosbuvir, comprising the step of reacting a compound of formula 2: wherein R.sub.1 and R.sub.2 can independently be hydrogen or halogen, provided that at least one of R.sub.1 and R.sub.2 is a halogen. ##STR00001##

Disclosed herein are a liver specific delivery (LSD)-based antiviral prodrug nucleoside cyclophosphate compound and uses thereof. Specifically, this application provides a compound of formula (I), or an isomer, a pharmaceutically acceptable salt, a hydrate, a solvate or a pharmaceutical composition thereof. This application also provides an application of the compound alone or in combination with other antiviral drugs in the treatment for viruses, particularly hepatitis C virus (HCV).

##STR00001##

The present invention relates to nucleotides, analogs of mRNA 5-end (cap) containing sulfur atom at the position 5 of 7-methylguanosine nucleoside. The disclosed compounds are recognized (bound and non-hydrolyzed) by DcpS enzyme (Decapping Scavenger), and thus may find therapeutic use as inhibitors thereof. DcpS is cap-specific enzyme with pyrophosphatase activity, which was identified as a therapeutic target in the treatment of spinal muscular atrophy (SMA). Some of the compounds disclosed have additional modifications in the phosphate chain, which modulate their affinity for DcpS enzyme. The present invention also relates to mRNAs modified at the 5 end with mRNA 5-end (cap) analogs containing 5-phosphorothiolate moiety, which mRNAs have an increased stability and translational activity in cellular conditions, to a method of their preparation, their uses, and to a pharmaceutical formulation containing them, wherein L.sup.1 and L.sup.2 are independently selected from the group comprising O and S, wherein at least one of L.sup.1 and L.sup.2 is not O.

##STR00001##

The present invention relates to nucleotides, analogs of mRNA 5-end (cap) containing sulfur atom at the position 5 of 7-methylguanosine nucleoside. The disclosed compounds are recognized (bound and non-hydrolyzed) by DcpS enzyme (Decapping Scavenger), and thus may find therapeutic use as inhibitors thereof. DcpS is cap-specific enzyme with pyrophosphatase activity, which was identified as a therapeutic target in the treatment of spinal muscular atrophy (SMA). Some of the compounds disclosed have additional modifications in the phosphate chain, which modulate their affinity for DcpS enzyme. The present invention also relates to mRNAs modified at the 5 end with mRNA 5-end (cap) analogs containing 5-phosphorothiolate moiety, which mRNAs have an increased stability and translational activity in cellular conditions, to a method of their preparation, their uses, and to a pharmaceutical formulation containing them, wherein L.sup.1 and L.sup.2 are independently selected from the group comprising O and S, wherein at least one of L.sup.1 and L.sup.2 is not O.

##STR00001##

The present disclosure provides procedures and intermediates for the preparation of Sofosbuvir, comprising the step of reacting a compound of formula 2: wherein R.sub.1 and R.sub.2 can independently be hydrogen or halogen, provided that at least one of R.sub.1 and R.sub.2 is a halogen.

##STR00001##

The present disclosure provides procedures and intermediates for the preparation of Sofosbuvir, comprising the step of reacting a compound of formula 2: wherein R.sub.1 and R.sub.2 can independently be hydrogen or halogen, provided that at least one of R.sub.1 and R.sub.2 is a halogen.

##STR00001##

The present invention relates to efficient processes useful in the preparation of fluorinated cyclic dinucleosides, such as [P(R)]-2-deoxy-2-fluoro-5-O[(R)-hydroxymercaptophosphinyl]-P-thio-?-D-arabino-adenylyl-(3.fwdarw.5)-3-deoxy-3-fluoroguanosine cyclic nucleotide, which is also known as (2R,5R,7R,8S,10R,12aR,14R,15S,15aR,16R)-7-(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)-14-(6-amino-9H-purin-9-yl)-15,16-difluoro-2, 10-bis(sulfanyl)octahydro-2H,10H, 12H-2?.sup.5,10?.sup.5-5,8-methanofuro[3,2-1][1, 3,6,9,11,2,10]pentaoxadiphosphacyclotetradecine-2,10-dione. The present invention also encompasses intermediates useful in the disclosed synthetic processes and the methods of their preparation.

##STR00001##

The invention relates to a method for preparing 3-O-amino-2-deoxyribonucleoside-5-triphosphate. It also relates to a solid support functionalized with at least one N-hydroxyphthalimide moiety and uses thereof for protecting 3-hydroxy group of a 2-deoxyribonucleoside during synthesis of a nucleoside or a derivative thereof.

The invention relates to a method for preparing 3-O-amino-2-deoxyribonucleoside-5-triphosphate. It also relates to a solid support functionalized with at least one N-hydroxyphthalimide moiety and uses thereof for protecting 3-hydroxy group of a 2-deoxyribonucleoside during synthesis of a nucleoside or a derivative thereof.