D-AMINO ACID COMPOUNDS FOR LIVER DISEASE
Provided herein are compounds, compositions and methods for the treatment of liver disease and conditions, 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.
1 - 2 . (canceled)
3 . A compound according to formula (II) or a pharmaceutically acceptable salt, solvate, tautomeric form or polymorphic form thereof:
Base is guanine, uracil, cytosine, adenine or a derivative thereof;
W is O;
Y is —OR 1 ;
R b1 is —CH 3 ;
R b2 is —Cl;
R 1 is phenyl;
R 10 is —CH 3
R 11 is ethyl, propyl, isopropyl, n-propyl, butyl, n-butyl, t-butyl, cyclopentyl, or benzyl;
R c is —OH;
R d is —H; and
R e is —H.
4 - 28 . (canceled)
29 . The compound of claim 3 , wherein said compound is according to the structure:
30 . The compound of claim 3 , wherein said compound is:
31 . The compound of claim 3 , wherein said compound is:
32 . The compound of claim 3 , wherein said compound is according to the structure:
33 . The compound according to claim 32 , wherein said compound is:
34 . The compound according to claim 32 , wherein said compound is:
35 . 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.
36 . The compound according to claim 35 , wherein said compound is according to the structure:
37 . The compound according to claim 35 , wherein said compound is
or a pharmaceutically acceptable salt, solvate, tautomeric form or polymorphic form thereof.
38 . The compound according to claim 37 , wherein said compound is
39 . A compound having the structure:
or a pharmaceutically acceptable salt, solvate, tautomeric form or polymorphic form thereof.
40 . A compound having the structure:
41 . A nucleoside composition comprising a compound according to Formula IIa or IIb:
or a pharmaceutically acceptable salt, solvate, tautomeric form or polymorphic form thereof, wherein said composition is substantially free of other stereoisomers of said compound:
wherein Base is guanine, uracil, cytosine, adenine or a derivative thereof;
W is O;
Y is —OR 1 ;
R 1 is phenyl;
R 10 is —CH 3 ;
R 11 is ethyl, propyl, isopropyl, n-propyl, butyl, n-butyl, t-butyl, or cyclopentyl;
R b1 is —CH 3 ;
R b2 is —Cl;
R c —OH;
R d is —H; and
R e is —H.
42 . The composition according to claim 41 , wherein said compound is:
43 . The composition according to claim 41 , wherein said compound is:
or a pharmaceutically acceptable salt, solvate, tautomeric form or polymorphic form thereof.
44 . The composition according to claim 43 , wherein said compound is:
45 . A pharmaceutical composition comprising a compound according to formula (II) or a pharmaceutically acceptable salt, solvate, tautomeric form or polymorphic form thereof:
wherein Base is guanine, uracil, cytosine, adenine or a derivative thereof;
W is O;
Y is —OR 1 ;
R 1 is phenyl;
R 10 is —CH 3 ;
R 11 is ethyl, propyl, isopropyl, n-propyl, butyl, n-butyl, t-butyl, or cyclopentyl;
R b1 is —CH 3 ;
R b2 is —Cl;
R c —OH;
R d is —H; and
R e is —H;
and a pharmaceutically acceptable carrier.
46 . The pharmaceutical composition of claim 45 , wherein said composition provides a therapeutically effective amount of said compound for treating a human infected with HCV.
47 . The pharmaceutical composition of claim 46 , wherein said compound is according to the structure:
or a pharmaceutically acceptable salt, solvate, tautomeric form or polymorphic form thereof.
48 . The pharmaceutical composition of claim 47 , wherein said compound is according to the structure:
49 . The pharmaceutical composition of claim 46 , wherein said compound is:
or a pharmaceutically acceptable salt, solvate, tautomeric form or polymorphic form thereof.
50 . The pharmaceutical composition of claim 49 , wherein said compound is:
51 . The pharmaceutical composition of claim 46 , wherein said compound is:
or a pharmaceutically acceptable salt, solvate, tautomeric form or polymorphic form thereof.
52 . The pharmaceutical composition of claim 51 , wherein said compound is:
53 . The pharmaceutical composition of claim 51 , wherein said compound is a designated enantiomer, and said composition is substantially free of other stereoisomers of said compound.
54 . The pharmaceutical composition of claim 52 , wherein said compound is a designated enantiomer, and said composition is substantially free of other stereoisomers of said compound.
55 . 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 formula (II) or a pharmaceutically acceptable salt, solvate, tautomeric form or polymorphic form thereof:
wherein Base is guanosine, uracil, cytosine, adenine or a derivative thereof;
W is O;
Y is —OR 1 ;
R 1 is phenyl;
R 10 is —CH 3 ;
R 11 is ethyl, propyl, isopropyl, n-propyl, butyl, n-butyl, t-butyl, or cyclopentyl;
R b1 is —CH 3 ;
R b2 is —Cl;
R c is —OH;
R d is —H; and
R e is —H.
56 . The method of claim 55 , wherein said compound is according to the structure:
or a pharmaceutically acceptable salt, solvate, tautomeric form or polymorphic form thereof.
57 . The method of claim 56 , wherein said compound is according to the structure:
58 . The method of claim 55 , wherein said compound is:
or a pharmaceutically acceptable salt, solvate, tautomeric form or polymorphic form thereof.
59 . The method of claim 58 , wherein said compound is:
60 . The method of claim 55 , wherein said compound is:
or a pharmaceutically acceptable salt, solvate, tautomeric form or polymorphic form thereof.
61 . The method of claim 60 , wherein said compound is:
62 . 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 pharmaceutical composition comprising a compound according to Formula IIa or IIb, or a pharmaceutically acceptable salt, solvate, tautomeric form or polymorphic form thereof:
wherein said composition is substantially free of other stereoisomers of said compound:
wherein Base is guanosine, uracil, cytosine, adenine or a derivative thereof;
W is O;
Y is —OR 1 ;
R 1 is phenyl;
R 10 is —CH 3 ;
R 11 is ethyl, propyl, isopropyl, n-propyl, butyl, n-butyl, t-butyl, or cyclopentyl;
R b1 is —CH 3 ;
R b2 is —Cl;
R c —OH;
R d is —H; and
R e is —H; and a pharmaceutically acceptable carrier.
63 . The method of claim 62 , wherein said compound is:
or a pharmaceutically acceptable salt, solvate, tautomeric form or polymorphic form thereof.
64 . The method of claim 63 , wherein said compound is:
65 . The method of claim 62 , wherein said compound is:
or a pharmaceutically acceptable salt, solvate, tautomeric form or polymorphic form thereof.
66 . The method of claim 65 , wherein said compound is: