4'-FLUORO NUCLOSIDES FOR THE TREATMENT OF HCV

摘要

Provided herein are compounds, compositions and methods for the treatment of Flaviviridae infections, including HCV infections. In certain embodiments, compounds and compositions of nucleoside derivatives are disclosed, which can be administered either alone or in combination with other anti-viral agents. In certain embodiments, the compounds are according to Formula 1501:;;or a pharmaceutically acceptable salt, solvate, stereoisomeric form, tautomeric form or polymorphic form thereof, wherein B, PD, RA, RB, RC, L, M and Z are as described herein.

主权项

1. A compound according to Formula 1501:or a pharmaceutically acceptable salt, solvate, stereoisomeric form, tautomeric form, or polymorphic form thereof, wherein:
B is a nucleobase; PD is W is S or O; each of X and Y is independently hydrogen, —OR1, —NR1R2, Of an N-linked or O-linked amino acid residue or an N-linked or O-linked residue of an amino acid derivative; Z is —H or —OH; or, in the alternative, X and Z, together with the atoms to which they are attached, combine to form a six-membered heterocyclic ring wherein X and Z together represent a single divalent —O—; and Y is hydrogen, —OR1, —NR1R2, an N-linked or O-linked amino acid residue or an N-linked or O-linked residue of an amino acid derivative; each of RA and RB is independently hydrogen, hydroxyl, alkyl, halo, cyano, azide, alkoxyl, or thiol; or, in the alternative, RA and RB, together with the atoms to which they are attached, combine to form a 3-10 membered carbocyclic or heterocyclic ring; RC is hydrogen or alkyl; L is —O— or —CH2—; M is —CH2—, —O— or —S—; R1 at each occurrence is independently hydrogen, alkyl, cycloalkyl, aryl, heteroaryl, arylalkyl, or heteroarylalkyl; and R2 at each occurrence is independently hydrogen or alkyl; provided that when B is uracil; Z and RA are each hydroxyl; L and M are each —O—; RB is methyl; and RC is hydrogen, then PD is other thanand
provided that when B is uracil or cytosine; Z and RA are each hydroxyl; L and M are each —O—; and RB and RC are hydrogen, then PD is other than