US2004067877A1PendingUtilityA1
2', 3'-Dideoxynucleoside analogues for the treatment or prevention of Flaviviridae infections
Priority: Aug 1, 2002Filed: Aug 1, 2003Published: Apr 8, 2004
Est. expiryAug 1, 2022(expired)· nominal 20-yr term from priority
A61K 31/7072A61K 38/21C07H 19/06A61P 31/00A61K 38/2066A61K 31/58A61K 31/553A61K 31/513A61K 31/7068
56
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Claims
Abstract
A method for the treatment or prevention of Flaviviridae infections, in particular, hepatitis C virus infection, in a host, and in particular, a human, is provided that includes administering an effective amount of a β-L- or β-D-2′,3′-dideoxynucleoside or a pharmaceutically acceptable salt or prodrug thereof, optionally in a pharmaceutically acceptable diluent or excipient.
Claims
exact text as granted — not AI-modifiedWe claim
1 . A method for the treatment of an HCV infection in a host, comprising administering an effective treatment amount of a 2′,3′-dideoxynucleoside of the formula:
or a pharmaceutically acceptable salt thereof, wherein
(i) X is O, S, S═O, SO 2 , NR 1 , N + R 1 R 2 , CH 2 , CHF and CR 3 R 4 ;
R 1 and R 2 are independently hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, or C 3-8 cycloalkyl;
R 3 and R 4 are independently hydrogen, halogen (F, Cl, Br, or I), OH or OR 5 ;
R 5 is hydrogen or a hydroxyl-protecting group, such as alkyl, acyl or silyl;
(ii) Y is NH 2 , NHR 6 , NR 6 R 7 , OH or OR 8
each R 6 , R 7 and R 8 is independently H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-8 cycloalkyl, cyclopropyl, or C 2-6 acyl;
(iii) Z is chosen from hydrogen, halogen (F, Cl, Br, or I), C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, CN, CF 3 , N 3 , NO 2 , aryl, heteroaryl and COR 9 ;
R 9 is chosen from H, OH, SH, C 1-6 alkyl, C 1-6 aminoalkyl, C 1-6 alkoxy and C 1-6 thioalkyl; and
(iv) R is hydrogen, phosphate; stabilized phosphate; acyl; —C(O)R 10 , alkyl; sulfonate ester; sulfonyl; a lipid; an amino acid; a carbohydrate; a peptide; a cholesterol; or other pharmaceutically acceptable leaving group, which, when administered in vivo, is capable of providing a compound wherein R is H or phosphate;
R 10 is a C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, monophosphate, diphosphate, triphosphate, or —P(O)(OR 11 ) 2 ;
each R 11 is independently hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl or a hydroxyl-protecting group;
optionally in a pharmaceutically acceptable carrier.
2 . The method of claim 1 , wherein Z is not hydrogen.
3 . The method of claim 1 , wherein Z is a halogen (F, Cl, Br, or I).
4 . The method of claim 3 , wherein Z is F.
5 . The method of claim 1 , wherein the 2′,3′-dideoxynucleoside is in the β-L-configuration.
6 . The method of claim 5 , wherein the β-L-2′,3′-dideoxynucleoside is enantiomerically enriched.
7 . The method of claim 5 , wherein the β-L-2′,3′-dideoxynucleoside is substantially free of the β-D-2′,3′-dideoxynucleoside.
8 . The method of claim 5 , wherein the β-L-2′,3′-dideoxynucleoside is in isolated form.
9 . A method for the treatment of an HCV infection in a host, comprising administering an effective treatment amount of a compound of the formula:
or a pharmaceutically acceptable salt thereof, wherein
Z′ is chosen from halogen (F, Cl, Br, or I), C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, CN, CF 3 , N 3 , NO 2 , aryl, heteroaryl and COR 9 ; and
R 9 is chosen from H, OH, SH, C 1-6 alkyl, C 1-6 aminoalkyl, C 1-6 alkoxy and C 1-6 thioalkyl.
optionally in a pharmaceutically acceptable carrier.
10 . A method for the treatment of an HCV infection in a host, comprising administering an effective treatment amount of a compound of the formula:
or a pharmaceutically acceptable salt thereof, wherein
(i) R 6 is H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-8 cycloalkyl, cyclopropyl, or C 2-6 acyl; and
(ii) R is hydrogen, phosphate; stabilized phosphate; acyl; —C(O)R 10 , alkyl; sulfonate ester; sulfonyl; a lipid; an amino acid; a carbohydrate; a peptide; a cholesterol; or other pharmaceutically acceptable leaving group, which, when administered in vivo, is capable of providing a compound wherein R is H or phosphate;
(iii) Z′ is chosen from halogen (F, Cl, Br, or I), C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, CN, CF 3 , N 3 , NO 2 , aryl, heteroaryl and COR 9 ; and
R 9 is chosen from H, OH, SH, C 1-6 alkyl, C 1-6 aminoalkyl, C 1-6 alkoxy and C 1-6 thioalkyl;
optionally in a pharmaceutically acceptable carrier.
11 . A method for the treatment of an HCV infection in a host, comprising administering an effective treatment amount of a compound of the formula:
or a pharmaceutically acceptable salt thereof, optionally in a pharmaceutically acceptable carrier.
12 . A method for the treatment of an HCV infection in a host, comprising administering an effective treatment amount of a compound of the formula:
or a pharmaceutically acceptable salt thereof,
(i) R 6 is H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, or C 3-8 cycloalkyl; and
(ii) R is hydrogen, phosphate; stabilized phosphate; acyl; —C(O)R 10 ; alkyl; sulfonate ester; sulfonyl; a lipid; an amino acid; a carbohydrate; a peptide; a cholesterol; or other pharmaceutically acceptable leaving group which when administered in vivo is capable of providing a compound wherein R is H or phosphate;
optionally in a pharmaceutically acceptable carrier.
13 . The method of any one of claims 10 , wherein the β-L-2′,3′-dideoxynucleoside is enantiomerically enriched.
14 . The method of any one of claims 10 , wherein the β-L-2′,3′-dideoxynucleoside is substantially free of the β-D-2′,3′-dideoxynucleoside.
15 . The method of any one of claims 10 , wherein the β-L-2′,3′-dideoxynucleoside is in isolated form.
16 . A method for reducing the biological activity of a Flaviviridae viral infection in a host comprising administering an effective treatment amount of a 2′,3′-dideoxynucleoside of the formula:
or a pharmaceutically acceptable salt thereof, wherein
(i) X is O, S, S═O, SO 2 , NR 1 , N + R 1 R 2 , CH 2 , CHF or CR 3 R 4 ;
R 1 and R 2 are independently hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, or C 3-8 cycloalkyl;
R 3 and R 4 are independently hydrogen, halogen (F, Cl, Br, or I), OH or OR 5 ;
R 5 is hydrogen or a hydroxyl protecting group such as alkyl, acyl or silyl;
(ii) Y is NH 2 , NHR 6 , NR 6 R 7 , OH or OR 8
each R 6 , R 7 and R 8 is independently H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-8 cycloalkyl, cyclopropyl, or C 2-6 acyl;
(iii) Z is chosen from hydrogen, halogen (F, Cl, Br, or I), C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, CN, CF 3 , N 3 , NO 2 , aryl, heteroaryl and COR 9 ;
R 9 is chosen from H, OH, SH, C 1-6 alkyl, C 1-6 aminoalkyl, C 1-6 alkoxy and C 1-6 thioalkyl; and
(iv) R is hydrogen, phosphate; acyl; —C(O)R 10 , alkyl; sulfonate ester; sulfonyl; a lipid; an amino acid; a carbohydrate; a peptide; a cholesterol; or other pharmaceutically acceptable leaving group, which, when administered in vivo, is capable of providing a compound wherein R is H or phosphate;
R 10 is a C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, monophosphate, diphosphate, triphosphate, or —P(O)(OR 11 ) 2 ;
each R 11 is independently hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl or a hydroxyl-protecting group;
optionally in a pharmaceutically acceptable carrier.
17 . The method of claim 16 , wherein Z is not hydrogen.
18 . The method of claim 16 , wherein Z is a halogen (F, Cl, Br, or I).
19 . The method of claim 18 , wherein Z is F.
20 . The method of claim 16 , wherein the 2′,3′-dideoxynucleoside is in the β-L-configuration.
21 . A method for reducing the biological activity of a Flaviviridae viral infection in a host comprising administering an effective treatment amount of a compound of the formula:
or a pharmaceutically acceptable salt thereof, wherein
Z′ is chosen from halogen (F, Cl, Br, or I), C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, CN, CF 3 , N 3 , NO 2 , aryl, heteroaryl and COR 9 ; and
R 9 is chosen from H, OH, SH, C 1-6 alkyl, C 1-6 aminoalkyl, C 1-6 alkoxy and C 1-6 thioalkyl.
optionally in a pharmaceutically acceptable carrier.
22 . A method for reducing the biological activity of a Flaviviridae viral infection in a host comprising administering an effective treatment amount of a compound of the formula:
or a pharmaceutically acceptable salt thereof, wherein
(i) R 6 is H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-8 cycloalkyl, cyclopropyl, or C 2-6 acyl; and
(ii) R is hydrogen, phosphate; acyl; —C(O)R 10 , alkyl; sulfonate ester; sulfonyl; a lipid; an amino acid; a carbohydrate; a peptide; a cholesterol; or other pharmaceutically acceptable leaving group, which, when administered in vivo, is capable of providing a compound wherein R is H or phosphate;
(iii) Z′ is chosen from halogen (F, Cl, Br, or I), C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, CN, CF 3 , N 3 , NO 2 , aryl, heteroaryl and COR 9 ; and
R 9 is chosen from H, OH, SH, C 1-6 alkyl, C 1-6 aminoalkyl, C 1-6 alkoxy and C 1-6 thioalkyl;
optionally in a pharmaceutically acceptable carrier.
23 . A method for reducing the biological activity of a Flaviviridae viral infection in a host comprising administering an effective treatment amount of a compound of the formula:
or a pharmaceutically acceptable salt thereof, optionally in a pharmaceutically acceptable carrier.
24 . A method for reducing the biological activity of a Flaviviridae viral infection in a host comprising administering an effective treatment amount of a compound of the formula:
or a pharmaceutically acceptable salt thereof,
(i) R 6 is H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, or C 3-8 cycloalkyl; and
(ii) R is hydrogen, phosphate; acyl; —C(O)R 10 , alkyl; sulfonate ester; sulfonyl; a lipid; an amino acid; a carbohydrate; a peptide; a cholesterol; or other pharmaceutically acceptable leaving group, which, when administered in vivo, is capable of providing a compound wherein R is H or phosphate;
optionally in a pharmaceutically acceptable carrier.
25 . The method according to claim 16 , wherein the Flaviviridae viral infection is an HCV infection.
26 . The method according to any one of claims 1 or 16 , further comprising administering in combination and/or alternation one or more other antiviral agent(s).
27 . The method according to claim 26 , wherein the antiviral agent is selected from the group consisting of ribavirin, interferon, PEGASYS (pegylated interferon alfa-2a), INFERGEN (interferon alfacon-1), OMNIFERON (natural interferon), ALBUFERON, REBIF (interferon beta-1a), Omega Interferon, Oral Interferon Alpha, Interferon gamma-1b, Interleukin-10, IP-501, Merimebodib VX-497, AMANTADINE (Symmetrel), HEPTAZYME, IDN-6556, XTL-002, HCV/MF59, CIVACIR, LEVOVIRIN, VIRAMIDINE, ZADAXIN (thymosin alfa-1), CEPLENE (histamine dihydrochloride), VX 950/LY 570310, ISIS 14803, IDN-6556 and JTK 003.
28 . The method according to any one of claims 1 or 16 , wherein the host is a human.
29 . The method according to any one of claims 1 or 16 , wherein the host is also infected with HIV and/or HBV.
30 . The method according to claim 29 , wherein the host is a human.
31 . A pharmaceutical composition for the treatment and/or prophylaxis of an HCV infection in a host, comprising an effective treatment amount of a 2′,3′-dideoxynucleoside of the formula:
or a pharmaceutically acceptable salt or prodrug thereof, wherein
(i) X is O, S, S═O, SO 2 , NR 1 , N + R 1 R 2 , CH 2 , CHF or CR 3 R 4 ;
R 1 and R 2 are independently hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, or C 3-8 cycloalkyl;
R 3 and R 4 are independently hydrogen, halogen (F, Cl, Br, or I), OH or OR 5 ;
R 5 is hydrogen or a hydroxyl protecting group such as alkyl, acyl or silyl;
(ii) Y is NH 2 , NHR 6 , NR 6 R 7 , OH or OR 8
each R 6 , R 7 and R 7 is independently H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-8 cycloalkyl, cyclopropyl, or C 2-6 acyl;
(iii) Z is chosen from hydrogen, halogen (F, Cl, Br, or I), C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, CN, CF 3 , N 3 , NO 2 , aryl, heteroaryl and COR 9 ;
R 9 is chosen from H, OH, SH, C 1-6 alkyl, C 1-6 aminoalkyl, C 1-6 alkoxy and C 1-6 thioalkyl; and
(iv) R is hydrogen, phosphate; acyl; —C(O)R 10 , alkyl; sulfonate ester; sulfonyl; a lipid; an amino acid; a carbohydrate; a peptide; a cholesterol; or other pharmaceutically acceptable leaving group, which, when administered in vivo, is capable of providing a compound wherein R is H or phosphate;
R 10 is a C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, monophosphate, diphosphate, triphosphate, or —P(O)(OR 11 ) 2 ;
each R 11 is independently hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl or a hydroxyl-protecting group;
together with pharmaceutically acceptable carrier.
32 . The pharmaceutical composition of claim 31 , wherein Z is not hydrogen.
33 . The pharmaceutical composition of claim 31 , wherein Z is a halogen (F, Cl, Br, or I).
34 . The pharmaceutical composition of claim 33 , wherein Z is F.
35 . The pharmaceutical composition of claim 31 , wherein the 2′,3′-dideoxynucleoside is in the β-L-configuration.
36 . The pharmaceutical composition of claim 35 , wherein the β-L-2′,3′-dideoxynucleoside is enantiomerically enriched.
37 . The pharmaceutical composition of claim 35 , wherein the β-L-2′,3′-dideoxynucleoside is substantially free of the β-D-2′,3′-dideoxynucleoside.
38 . The pharmaceutical composition of claim 35 , wherein the β-L-2′,3′-dideoxynucleoside is in isolated form.
39 . A pharmaceutical composition for the treatment and/or prophylaxis of an HCV infection in a host, comprising an effective amount of a compound of the formula:
or a pharmaceutically acceptable salt or prodrug thereof, wherein
Z′ is chosen from halogen (F, Cl, Br, or I), C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, CN, CF 3 , N 3 , NO 2 , aryl, heteroaryl and COR 9 ; and
R 9 is chosen from H, OH, SH, C 1-6 alkyl, C 1-6 aminoalkyl, C 1-6 alkoxy and C 1-6 thioalkyl.
together with a pharmaceutically acceptable carrier.
40 . A pharmaceutical composition for the treatment and/or prophylaxis of an HCV infection in a host, comprising an effective amount of a compound of the formula:
or a pharmaceutically acceptable salt or prodrug thereof, wherein
(i) R 6 is H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-8 cycloalkyl, cyclopropyl, or C 2-6 acyl; and
(ii) R is hydrogen, phosphate; acyl; —C(O)R 10 , alkyl; sulfonate ester; sulfonyl; a lipid; an amino acid; a carbohydrate; a peptide; a cholesterol; or other pharmaceutically acceptable leaving group, which, when administered in vivo, is capable of providing a compound wherein R is H or phosphate;
(iii) Z′ is chosen from halogen (F, Cl, Br, or I), C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, CN, CF 3 , N 3 , NO 2 , aryl, heteroaryl and COR 9 ; and
R 9 is chosen from H, OH, SH, C 1-6 alkyl, C 1-6 aminoalkyl, C 1-6 alkoxy and C 1-6 thioalkyl;
together with a pharmaceutically acceptable carrier.
41 . A pharmaceutical composition for the treatment and/or prophylaxis of an HCV infection in a host, comprising an effective amount of a compound of the formula:
or a pharmaceutically acceptable salt or prodrug thereof, together with a pharmaceutically acceptable carrier.
42 . A pharmaceutical composition for the treatment and/or prophylaxis of an HCV infection in a host, comprising an effective amount of a compound of the formula:
or a pharmaceutically acceptable salt or prodrug thereof,
(i) R 6 is H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, or C 3-8 cycloalkyl; and
(ii) R is hydrogen, phosphate; acyl; —C(O)R 10 , alkyl; sulfonate ester; sulfonyl; a lipid; an amino acid; a carbohydrate; a peptide; a cholesterol; or other pharmaceutically acceptable leaving group, which, when administered in vivo, is capable of providing a compound wherein R is H or phosphate;
together with a pharmaceutically acceptable carrier.
43 . The pharmaceutical composition of any one of claims 40 , wherein the β-L-2′,3′-dideoxynucleoside is enantiomerically enriched.
44 . The pharmaceutical composition of any one of claims 40 , wherein the β-L-2′,3′-dideoxynucleoside is substantially free of the β-D-2′,3′-dideoxynucleoside.
45 . The pharmaceutical composition of any one of claims 40 , wherein the β-L-2′,3′-dideoxynucleoside is in an isolated form.
46 . A pharmaceutical composition for reducing the biological activity of a Flaviviridae viral infection in a host comprising an effective amount of a 2′,3′-dideoxynucleoside of the formula:
or a pharmaceutically acceptable salt or prodrug thereof, wherein
(i) X is O, S, S═O, SO 2 , NR 1 , N + R 1 R 2 , CH 2 , CHF or CR 3 R 4 ;
R 1 and R 2 are independently hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, or C 3-8 cycloalkyl;
R 3 and R 4 are independently hydrogen, halogen (F, Cl, Br, or I), OH or OR 5 ;
R 5 is hydrogen or a hydroxyl protecting group such as alkyl, acyl or silyl;
(ii) Y is NH 2 , NHR 6 , NR 6 R 7 , OH or OR 8
each R 6 , R 7 and R 7 is independently H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-8 cycloalkyl, cyclopropyl, or C 2-6 acyl;
(iii) Z is chosen from hydrogen, halogen (F, Cl, Br, or I), C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, CN, CF 3 , N 3 , NO 2 , aryl, heteroaryl and COR 9 ;
R 9 is chosen from H, OH, SH, C 1-6 alkyl, C 1-6 aminoalkyl, C 1-6 alkoxy and C 1-6 thioalkyl; and
(iv) R is hydrogen, phosphate; acyl; —C(O)R 10 , alkyl; sulfonate ester; sulfonyl; a lipid; an amino acid; a carbohydrate; a peptide; a cholesterol; or other pharmaceutically acceptable leaving group, which, when administered in vivo, is capable of providing a compound wherein R is H or phosphate;
R 10 is a C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, monophosphate, diphosphate, triphosphate, or —P(O)(OR 11 ) 2 ;
each R 11 is independently hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl or a hydroxyl-protecting group;
together with a pharmaceutically acceptable carrier.
47 . The pharmaceutical composition of claim 46 , wherein Z is not hydrogen.
48 . The pharmaceutical composition of claim 46 , wherein Z is a halogen (F, Cl, Br, or I).
49 . The pharmaceutical composition of claim 48 , wherein Z is F.
50 . The pharmaceutical composition of claim 46 , wherein the 2′,3′-dideoxynucleoside is in the β-L-configuration.
51 . A pharmaceutical composition for reducing the biological activity of a Flaviviridae viral infection in a host comprising an effective amount of a compound of the formula:
or a pharmaceutically acceptable salt or prodrug thereof, wherein
Z′ is chosen from halogen (F, Cl, Br, or I), C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, CN, CF 3 , N 3 , NO 2 , aryl, heteroaryl and COR 9 ; and
R 9 is chosen from H, OH, SH, C 1-6 alkyl, C 1-6 aminoalkyl, C 1-6 alkoxy and C 1-6 thioalkyl.
together with a pharmaceutically acceptable carrier.
52 . A pharmaceutical composition for reducing the biological activity of a Flaviviridae viral infection in a host comprising an effective amount of a compound of the formula:
or a pharmaceutically acceptable salt or prodrug thereof, wherein
(i) R 6 is H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-8 cycloalkyl, cyclopropyl, or C 2-6 acyl; and
(ii) R is hydrogen, phosphate; acyl; —C(O)R 10 , alkyl; sulfonate ester; sulfonyl; a lipid; an amino acid; a carbohydrate; a peptide; a cholesterol; or other pharmaceutically acceptable leaving group, which, when administered in vivo, is capable of providing a compound wherein R is H or phosphate;
(iii) Z′ is chosen from halogen (F, Cl, Br, or I), C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, CN, CF 3 , N 3 , NO 2 , aryl, heteroaryl and COR 9 ; and
R 9 is chosen from H, OH, SH, C 1-6 alkyl, C 1-6 aminoalkyl, C 1-6 alkoxy and C 1-6 thioalkyl;
together with a pharmaceutically acceptable carrier.
53 . A pharmaceutical composition for reducing the biological activity of a Flaviviridae viral infection in a host comprising an effective amount of a compound of the formula:
or a pharmaceutically acceptable salt or prodrug thereof, together with a pharmaceutically acceptable carrier.
54 . A pharmaceutical composition for reducing the biological activity of a Flaviviridae viral infection in a host comprising an effective amount of a compound of the formula:
or a pharmaceutically acceptable salt or prodrug thereof,
(i) R 6 is H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, or C 3-8 cycloalkyl; and
(ii) R is hydrogen, phosphate; acyl; —C(O)R 10 , alkyl; sulfonate ester; sulfonyl; a lipid; an amino acid; a carbohydrate; a peptide; a cholesterol; or other pharmaceutically acceptable leaving group, which, when administered in vivo, is capable of providing a compound wherein R is H or phosphate;
together with a pharmaceutically acceptable carrier.
55 . The pharmaceutical composition according to claim 52 , wherein the Flaviviridae viral infection is an HCV infection.
56 . The pharmaceutical composition according to any one of claims 31 or 46 , further comprising one or more other antiviral agent(s).
57 . The pharmaceutical composition according to claim 56 , wherein the antiviral agent is selected from the group consisting of ribavirin, interferon, PEGASYS (pegylated interferon alfa-2a), INFERGEN (interferon alfacon-1), OMNIFERON (natural interferon), ALBUFERON, REBIF (interferon beta-1a), Omega Interferon, Oral Interferon Alpha, Interferon gamma-1b, Interleukin-10, IP-501, Merimebodib VX-497, AMANTADINE (Symmetrel), HEPTAZYME , IDN-6556, XTL-002, HCV/MF59, CIVACIR, LEVOVIRIN, VIRAMIDINE, ZADAXIN (thymosin alfa-1), CEPLENE (histamine dihydrochloride), VX 950/LY 570310, ISIS 14803, IDN-6556 and JTK 003.
58 . The pharmaceutical composition according to any one of claims 31 or 46 , wherein the host is a human.
59 . The pharmaceutical composition according to any one of claims 32 or 46 , wherein the host is also infected with HIV and/or HBV.
60 . The pharmaceutical composition according to claim 59 , wherein the host is a human.Join the waitlist — get patent alerts
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