2'-CHLORO NUCLEOSIDE ANALOGS FOR HCV INFECTION
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 2′-chloro nucleosides according to Formula 2001: or a pharmaceutically acceptable salt, solvate, stereoisomeric form, tautomeric form or polymorphic form thereof, wherein B, Z and PD are as described herein.
1 - 2 . (canceled)
3 . A compound according to Formula III:
or a pharmaceutically acceptable salt, solvate, tautomeric form or polymorphic form thereof;
wherein B is a nucleobase;
R 1 is phenyl;
X is an N-linked amino acid ester; and
W is O.
4 - 41 . (canceled)
42 . The compound according to claim 3 , wherein said compound is according to the structure:
or a pharmaceutically acceptable salt, solvate, tautomeric form or polymorphic form thereof.
43 . The compound according to claim 42 , wherein said compound is according to the structure:
44 . The compound according to claim 3 , wherein said compound is:
or a pharmaceutically acceptable salt, solvate, tautomeric form or polymorphic form thereof.
45 . The compound according to claim 44 , wherein said compound is:
46 . The compound according to claim 3 , wherein said compound is:
or a pharmaceutically acceptable salt, solvate, tautomeric form or polymorphic form thereof.
47 . The compound of claim 46 , wherein said compound is:
48 . A nucleoside composition comprising a compound selected from the group consisting of:
wherein said compound is a designated enantiomer and said composition is substantially free of other stereoisomers of said compound.
49 . A pharmaceutical composition comprising a compound of claim 3 or a pharmaceutically acceptable salt, solvate, tautomeric form or polymorphic form thereof; and a pharmaceutically acceptable carrier.
50 . The pharmaceutical composition according to claim 49 , wherein said compound is according to the structure:
or a pharmaceutically acceptable salt, solvate, tautomeric form or polymorphic form thereof.
51 . The pharmaceutical composition according to claim 50 , wherein said compound is according to the structure:
52 . The pharmaceutical composition according to claim 49 , wherein said compound is:
or a pharmaceutically acceptable salt, solvate, tautomeric form or polymorphic form thereof.
53 . The pharmaceutical composition according to claim 52 , wherein said compound is:
54 . The pharmaceutical composition according to claim 53 , wherein said compound is a designated enantiomer, and said composition is substantially free of other stereoisomers of said compound.
55 . The pharmaceutical composition according to claim 49 , wherein said compound is:
or a pharmaceutically acceptable salt, solvate, tautomeric form or polymorphic form thereof.
56 . The pharmaceutical composition of claim 55 , wherein said compound is:
57 . The pharmaceutical composition according to claim 56 , wherein said compound is a designated enantiomer, and said composition is substantially free of other stereoisomers of said compound.
58 . A method for the treatment of a human infected with a hepatitis C virus, comprising the administration to said human an effective amount of a compound according to claim 3 or a pharmaceutically acceptable salt, solvate, tautomeric form or polymorphic form thereof.
59 . The method according to claim 58 , wherein said compound is according to the structure:
or a pharmaceutically acceptable salt, solvate, tautomeric form or polymorphic form thereof.
60 . The method according to claim 59 , wherein said compound is according to the structure:
61 . The method according to claim 58 , wherein said compound is:
or a pharmaceutically acceptable salt, solvate, tautomeric form or polymorphic form thereof.
62 . The method according to claim 61 , wherein said compound is:
63 . The method according to claim 58 , wherein said compound is:
or a pharmaceutically acceptable salt, solvate, tautomeric form or polymorphic form thereof.
64 . The method according to claim 63 , wherein said compound is:
65 . The method of claim 58 , wherein the compound is administered in combination with a second anti-viral agent selected from the group consisting of an interferon, a nucleotide analogue, a polymerase inhibitor, an NS3 protease inhibitor, an NS5A inhibitor, an entry inhibitor, a non-nucleoside polymerase inhibitor, a cyclosporine immune inhibitor, an NS4A antagonist, an NS4B-RNA binding inhibitor, a locked nucleic acid mRNA inhibitor, a cyclophilin inhibitor, and combinations thereof.
66 . The method of claim 65 , wherein said compound is
67 . The method of claim 66 , wherein said second anti-viral agent is an NS3 protease inhibitor.
68 . The method of claim 66 , wherein said second anti-viral agent is an NS5A inhibitor.