MODIFIED FLUORINATED NUCLEOSIDE ANALOGUES
The disclosed invention provides compositions and methods of treating a Flaviviridae infection, including hepatitis C virus, West Nile Virus, yellow fever virus, and a rhinovirus infection in a host, including animals, and especially humans, using a (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleosides, or a pharmaceutically acceptable salt or prodrug thereof.
1 - 129 . (canceled)
130 . A (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside (β-D or β-L) or its pharmaceutically acceptable salt of the structure:
wherein the base is a purine base represented by the following formula:
X is O, S, CH 2 , Se, NH, N-alkyl, CHW (R, S, or racemic), C(W) 2 , wherein W is F, Cl, Br, or I;
R 1 and R 7 are independently H, phosphate, including monophosphate, diphosphate, triphosphate, or a stabilized phosphate prodrug, H-phosphonate, including stabilized H-phosphonates, acyl, including optionally substituted phenyl and lower acyl, alkyl, including lower alkyl, O-substituted carboxyalkylamino or its peptide derivatives, sulfonate ester, including alkyl or arylalkyl sulfonyl, including methanesulfonyl and benzyl, wherein the phenyl group is optionally substituted, a lipid, including a phospholipid, an L or D-amino acid (or racemic mixture), 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 1 is H or phosphate; R 2 is H or phosphate; R 1 and R 2 or R 7 can also be linked with cyclic phosphate group;
R 2 and R 2′ are independently H, C 1-4 allyl, C 1-4 alkenyl, C 1-4 alkynyl, vinyl, N 3 , CN, Cl, Br, F, I, NO2, C(O)O(C 1-4 alkyl), C(O)O(C 1-4 alkyl), C(O)O(C 1-4 alkynyl), C(O)O(C 1-4 alkenyl), O(C 1-4 acyl), O(C 1-4 alkyl), O(C 1-4 alkenyl), S(C 1-4 acyl), S(C 1-4 alkyl), S(C 1-4 alkynyl), S(C 1-4 alkenyl), SO(C 1-4 acyl), SO(C 1-4 alkyl), SO(C 1-4 alkynyl), SO(C 1-4 alkenyl), SO 2 (C 1-4 acyl), SO 2 (C 1-4 allyl), SO 2 (C 1-4 alkynyl), SO 2 (C 1-4 alkenyl), O 3 S(C 1-4 acyl), O 3 S(C 1-4 alkyl), O 3 S(C 1-4 alkenyl), NH 2 , NH(C 1-4 alkyl), NH(C 1-4 alkenyl), NH(C 1-4 alkynyl), NH(C 1-4 acyl), N(C 1-4 alkyl) 2 , N(C 1-18 acyl) 2 , wherein alkyl, alkynyl, alkenyl and vinyl are optionally substituted by N 3 , CN, one to three halogen (Cl, Br, F, I), NO 2 , C(O)O(C 1-4 alkyl), C(O)O(C 1-4 alkyl), C(O)O(C 1-4 alkynyl), C(O)O(C 1-4 alkenyl), O(C 1-4 acyl), O(C 1-4 alkyl), O(C 1-4 alkenyl), S(C 1-4 acyl), S(C 1-4 allyl), S(C 1-4 alkynyl), S(C 1-4 alkenyl), SO(C 1-4 acyl), SO(C 1-4 alkyl), SO(C 1-4 alkynyl), SO(C 1-4 alkenyl), SO 2 (C 1-4 acyl), SO 2 (C 1-4 alkyl), SO 2 (C 1-4 alkynyl), SO 2 (C 1-4 alkenyl), O 3 S(C 1-4 acyl), O 3 S(C 1-4 alkyl), O 3 S(C 1-4 alkenyl), NH 2 , NH(C 1-4 alkyl), NH(C 1-4 alkenyl), NH(C 1-4 alkynyl), NH(C 1-4 acyl), N(C 1-4 alkyl) 2 , N(C 1-4 acyl) 2 , OR 7 ; R 2 and R 2 ′ can be linked together to form a vinyl optionally substituted by one or two of N 3 , CN, Cl, Br, F, I, NO 2 ;
R 6 is an optionally substituted alkyl (including lower alkyl), cyano (CN), CH 3 , OCH 3 , OCH 2 CH 3 , hydroxy methyl (CH 2 OH), fluoromethyl (CH 2 F), azido (N 3 ), CHCN, CH 2 N 3 , CH 2 NH 2 , CH 2 NHCH 3 , CH 2 N(CH 3 ) 2 , alkyne (optionally substituted), or fluoro;
R 4 and R 5 are independently H, halogen including F, Cl, Br, I, OH, OR′, SH, SR′, NH 2 , NHR′, NR′ 2 , lower alkyl of C 1 -C 6 , halogenated (F, Cl, Br, I) lower allyl of C 1 -C 6 , lower alkenyl of C 2 -C 6 , halogenated (F, Cl, Br, I) lower alkenyl of C 2 -C 6 , lower alkynyl of C 2 -C 6 such as C≡CH, halogenated (F, Cl, Br, I) lower alkynyl of C 2 -C 6 , lower alkoxy of C 1 -C 6 such as CH 2 OH and CH 2 CH 2 OH, halogenated (F, Cl, Br, I) lower alkoxy of C 1 -C 6 , lower hydroxyalkyl, CO 2 H, CO 2 R′, CONH 2 , CONHR′, CONR′ 2 , CH═CHCO 2 H, CH═CHCO 2 R′; and
R′ is an optionally substituted alkyl of C 1 -C 12 , cycloalkyl, optionally substituted alkynyl of C 2 -C 6 , optionally substituted lower alkenyl of C 2 -C 6 or optionally substituted acyl.
when n is 1, then R 4 is ═O.
when n is 0, then a double bond exists between position 1 and position 6.
131 . The (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside (β-D) of claim 130 or its pharmaceutically acceptable salt thereof,
wherein the Base is represented by the following formula:
when n is 0, then R 4 is NH 2 , R 5 is H and a double bond exists between position 1 and position 6; when n is 1, then R 4 is ═O and R 5 is NH 2 .
132 . A (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside (β-D or β-L) or its pharmaceutically acceptable salt of the structure:
wherein the base is a purine base;
X is O, S, CH 2 , Se, NH, N-alkyl, CHW (R, S, or racemic), C(W) 2 , wherein W is F, Cl, Br, or I;
R 1 and R 7 are independently H, phosphate, including monophosphate, diphosphate, triphosphate, or a stabilized phosphate prodrug, H-phosphonate, including stabilized H-phosphonates, acyl, including optionally substituted phenyl and lower acyl, alkyl, including lower allyl, O-substituted carboxyalkylamino or its peptide derivatives, sulfonate ester, including alkyl or arylalkyl sulfonyl, including methanesulfonyl and benzyl, wherein the phenyl group is optionally substituted, a lipid, including a phospholipid, an L or D-amino acid (or racemic mixture), 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 1 is H or phosphate; R 2 is H or phosphate; R 1 and R 2 or R 7 can also be linked with cyclic phosphate group.
133 . The (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside (β-D) of claim 132 or its pharmaceutically acceptable salt thereof,
wherein the Base is represented by the following formula:
when n is 0, then R 4 is NH 2 , R 5 is H and a double bond exists between position 1 and position 6; when n is 1, then R 4 is ═O and R 5 is NH 2 .
134 . A (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside (β-D) or its pharmaceutically acceptable salt thereof of the formula:
wherein
R 1 and R 7 are independently H, phosphate, including monophosphate, diphosphate, triphosphate, or a stabilized phosphate prodrug, H-phosphonate, including stabilized H-phosphonates, acyl, including optionally substituted phenyl and lower acyl, alkyl, including lower alkyl, O-substituted carboxyalkylamino or its peptide derivatives, sulfonate ester, including alkyl or arylalkyl sulfonyl, including methanesulfonyl and benzyl, wherein the phenyl group is optionally substituted, a lipid, including a phospholipid, an L or D-amino acid (or racemic mixture), 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 1 or R 7 is independently H or phosphate; R 1 and R 7 can also be linked with cyclic phosphate group; and
R 6 is an optionally substituted alkyl (including lower allyl), cyano (CN), CH 3 , OCH 3 , OCH 2 CH 3 , hydroxy methyl (CH 2 OH), fluoromethyl (CH 2 F), azido (N 3 ), CHCN, CH 2 N 3 , CH 2 NH 2 , CH 2 NHCH 3 , CH 2 N(CH 3 ) 2 , alkyne (optionally substituted), or fluoro.
135 . A (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside (β-D) or its pharmaceutically acceptable salt thereof of the formula:
136 . A (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside (β-D) or its pharmaceutically acceptable salt thereof of the formula:
wherein
R 1 is H, phosphate, including monophosphate, diphosphate, triphosphate, or a stabilized phosphate prodrug, H-phosphonate, including stabilized H-phosphonates, acyl, including optionally substituted phenyl and lower acyl, alkyl, including lower alkyl, O-substituted carboxyalkylamino or its peptide derivatives, sulfonate ester, including alkyl or arylalkyl sulfonyl, including methanesulfonyl and benzyl, wherein the phenyl group is optionally substituted, a lipid, including a phospholipid, an L or D-amino acid (or racemic mixture), 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 1 is H or phosphate.
137 . A (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside (β-D) or its pharmaceutically acceptable salt thereof of the formula:
138 . A pharmaceutical composition comprising the nucleoside of claim 130 or its pharmaceutically acceptable salt and a pharmaceutically acceptable carrier.
139 . A pharmaceutical composition comprising the nucleoside of claim 131 or its pharmaceutically acceptable salt and a pharmaceutically acceptable carrier.
140 . A pharmaceutical composition comprising the nucleoside of claim 132 or its pharmaceutically acceptable salt and a pharmaceutically acceptable carrier.
141 . A pharmaceutical composition comprising the nucleoside of claim 133 or its pharmaceutically acceptable salt and a pharmaceutically acceptable carrier.
142 . A pharmaceutical composition comprising a (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside (β-D or β-L), or its pharmaceutically acceptable salt thereof, in a pharmaceutically acceptable carrier, of the formula:
wherein
R 1 and R 7 are independently H, phosphate, including monophosphate, diphosphate, triphosphate, or a stabilized phosphate prodrug, H-phosphonate, including stabilized H-phosphonates, acyl, including optionally substituted phenyl and lower acyl, allyl, including lower alkyl, O-substituted carboxyalkylamino or its peptide derivatives, sulfonate ester, including alkyl or arylalkyl sulfonyl, including methanesulfonyl and benzyl, wherein the phenyl group is optionally substituted, a lipid, including a phospholipid, an L or D-amino acid (or racemic mixture), 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 1 or R 7 is independently H or phosphate; R 1 and R 7 can also be linked with cyclic phosphate group; and
R 6 is an optionally substituted allyl (including lower alkyl), cyano (CN), CH 3 , OCH 3 , OCH 2 CH 3 , hydroxy methyl (CH 2 OH), fluoromethyl (CH 2 F), azido (N 3 ), CHCN, CH 2 N 3 , CH 2 NH 2 , CH 2 NHCH 3 , CH 2 N(CH 3 ) 2 , alkyne (optionally substituted), or fluoro.
143 . A pharmaceutical composition comprising a (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside (β-D or β-L), or its pharmaceutically acceptable salt thereof in a pharmaceutically acceptable carrier of the formula:
144 . A pharmaceutical composition comprising a (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside (β-D), or its pharmaceutically acceptable salt thereof in a pharmaceutically acceptable carrier of the formula:
wherein
R 1 is H, phosphate, including monophosphate, diphosphate, triphosphate, or a stabilized phosphate prodrug, H-phosphonate, including stabilized H-phosphonates, acyl, including optionally substituted phenyl and lower acyl, alkyl, including lower alkyl, O-substituted carboxyalkylamino or its peptide derivatives, sulfonate ester, including alkyl or arylalkyl sulfonyl, including methanesulfonyl and benzyl, wherein the phenyl group is optionally substituted, a lipid, including a phospholipid, an L or D-amino acid (or racemic mixture), 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 1 is H or phosphate.
145 . A pharmaceutical composition comprising a (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside (β-D), or its pharmaceutically acceptable salt thereof in a pharmaceutically acceptable carrier of the formula:
146 . A method for the treatment or prophylaxis of Hepatitis C infection comprising administering to a host an antivirally effective amount of the nucleoside of claim 130 or its pharmaceutically acceptable salt optionally in a pharmaceutically acceptable carrier.
147 . A method for the treatment or prophylaxis of Hepatitis C infection comprising administering to a host an antivirally effective amount of the nucleoside of claim 131 or its pharmaceutically acceptable salt optionally in a pharmaceutically acceptable carrier.
148 . A method for the treatment or prophylaxis of Hepatitis C infection comprising administering to a host an antivirally effective amount of the nucleoside of claim 132 or its pharmaceutically acceptable salt optionally in a pharmaceutically acceptable carrier.
149 . A method for the treatment or prophylaxis of Hepatitis C infection comprising administering to a host an antivirally effective amount of the nucleoside of claim 133 or its pharmaceutically acceptable salt optionally in a pharmaceutically acceptable carrier.
150 . A method for the treatment or prophylaxis of Hepatitis C infection comprising administering to a host an antivirally effective amount of a (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside (β-D) or its pharmaceutically acceptable salt thereof of the formula:
wherein
R 1 and R 7 are independently H, phosphate, including monophosphate, diphosphate, triphosphate, or a stabilized phosphate prodrug, H-phosphonate, including stabilized H-phosphonates, acyl, including optionally substituted phenyl and lower acyl, alkyl, including lower alkyl, O-substituted carboxyalkylamino or its peptide derivatives, sulfonate ester, including alkyl or arylalkyl sulfonyl, including methanesulfonyl and benzyl, wherein the phenyl group is optionally substituted, a lipid, including a phospholipid, an L or D-amino acid (or racemic mixture), 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 1 or R 7 is independently H or phosphate; R 1 and R 7 can also be linked with cyclic phosphate group; and
R 6 is an optionally substituted alkyl (including lower alkyl), cyano (CN), CH 3 , OCH 3 , OCH 2 CH 3 , hydroxy methyl (CH 2 OH), fluoromethyl (CH 2 F), azido (N 3 ), CHCN, CH 2 N 3 , CH 2 NH 2 , CH 2 NHCH 3 , CH 2 N(CH 3 ) 2 , alkyne (optionally substituted), or fluoro.
optionally in a pharmaceutically acceptable carrier.
151 . A method for the treatment or prophylaxis of Hepatitis C infection comprising administering to a host an antivirally effective amount of a (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside (β-D) or its pharmaceutically acceptable salt thereof of the formula:
optionally in a pharmaceutically acceptable carrier.
152 . A method for the treatment or prophylaxis of Hepatitis C infection comprising administering to a host an antivirally effective amount of a (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside (β-D) or its pharmaceutically acceptable salt thereof of the formula:
wherein
R 1 is H, phosphate, including monophosphate, diphosphate, triphosphate, or a stabilized phosphate prodrug, H-phosphonate, including stabilized H-phosphonates, acyl, including optionally substituted phenyl and lower acyl, alkyl, including lower alkyl, O-substituted carboxyalkylamino or its peptide derivatives, sulfonate ester, including alkyl or arylalkyl sulfonyl, including methanesulfonyl and benzyl, wherein the phenyl group is optionally substituted, a lipid, including a phospholipid, an L or D-amino acid (or racemic mixture), 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 1 is H or phosphate.
optionally in a pharmaceutically acceptable carrier.
153 . A method for the treatment or prophylaxis of Hepatitis C infection comprising administering to a host an antivirally effective amount of a (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside (β-D) or its pharmaceutically acceptable salt thereof of the formula:
optionally in a pharmaceutically acceptable carrier.
154 . A method for the treatment or prophylaxis of Rhinovirus infection comprising administering to a host an antivirally effective amount of the nucleoside of claim 130 or its pharmaceutically acceptable salt optionally in a pharmaceutically acceptable carrier.
155 . A method for the treatment or prophylaxis of Rhinovirus infection comprising administering to a host an antivirally effective amount of the nucleoside of claim 131 or its pharmaceutically acceptable salt optionally in a pharmaceutically acceptable carrier.
156 . A method for the treatment or prophylaxis of Rhinovirus infection comprising administering to a host an antivirally effective amount of the nucleoside of claim 132 or its pharmaceutically acceptable salt optionally in a pharmaceutically acceptable carrier.
157 . A method for the treatment or prophylaxis of Rhinovirus infection comprising administering to a host an antivirally effective amount of the nucleoside of claim 133 or its pharmaceutically acceptable salt optionally in a pharmaceutically acceptable carrier.
158 . A method for the treatment or prophylaxis of Rhinovirus infection comprising administering to a host an antivirally effective amount of a (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside (β-D) or its pharmaceutically acceptable salt thereof of the formula:
wherein
R 1 and R 7 are independently H, phosphate, including monophosphate, diphosphate, triphosphate, or a stabilized phosphate prodrug, H-phosphonate, including stabilized H-phosphonates, acyl, including optionally substituted phenyl and lower acyl, alkyl, including lower alkyl, O-substituted carboxyalkylamino or its peptide derivatives, sulfonate ester, including alkyl or arylalkyl sulfonyl, including methanesulfonyl and benzyl, wherein the phenyl group is optionally substituted, a lipid, including a phospholipid, an L or D-amino acid (or racemic mixture), 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 1 or R 7 is independently H or phosphate; R 1 and R 7 can also be linked with cyclic phosphate group; and
R 6 is an optionally substituted alkyl (including lower alkyl), cyano (CN), CH 3 , OCH 3 , OCH 2 CH 3 , hydroxy methyl (CH 2 OH), fluoromethyl (CH 2 F), azido (N 3 ), CHCN, CH 2 N 3 , CH 2 NH 2 , CH 2 NHCH 3 , CH 2 N(CH 3 ) 2 , alkyne (optionally substituted), or fluoro.
optionally in a pharmaceutically acceptable carrier.
159 . A method for the treatment or prophylaxis of Rhinovirus infection comprising administering to a host an antivirally effective amount of a (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside (β-D) or its pharmaceutically acceptable salt thereof of the formula:
optionally in a pharmaceutically acceptable carrier.
160 . A method for the treatment or prophylaxis of Rhinovirus infection comprising administering to a host an antivirally effective amount of a (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside (β-D) or its pharmaceutically acceptable salt thereof of the formula:
wherein
R 1 is H, phosphate, including monophosphate, diphosphate, triphosphate, or a stabilized phosphate prodrug, H-phosphonate, including stabilized H-phosphonates, acyl, including optionally substituted phenyl and lower acyl, alkyl, including lower alkyl, O-substituted carboxyalkylamino or its peptide derivatives, sulfonate ester, including alkyl or arylalkyl sulfonyl, including methanesulfonyl and benzyl, wherein the phenyl group is optionally substituted, a lipid, including a phospholipid, an L or D-amino acid (or racemic mixture), 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 1 is H or phosphate.
optionally in a pharmaceutically acceptable carrier.
161 . A method for the treatment or prophylaxis of Rhinovirus infection comprising administering to a host an antivirally effective amount of a (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside (β-D) or its pharmaceutically acceptable salt thereof of the formula:
optionally in a pharmaceutically acceptable carrier.
162 . A method for the treatment or prophylaxis of Yellow Fever Virus infection comprising administering to a host an antivirally effective amount of the nucleoside of claim 130 or its pharmaceutically acceptable salt optionally in a pharmaceutically acceptable carrier.
163 . A method for the treatment or prophylaxis of Yellow Fever Virus infection comprising administering to a host an antivirally effective amount of the nucleoside of claim 131 or its pharmaceutically acceptable salt optionally in a pharmaceutically acceptable carrier.
164 . A method for the treatment or prophylaxis of Yellow Fever Virus infection comprising administering to a host an antivirally effective amount of the nucleoside of claim 132 or its pharmaceutically acceptable salt optionally in a pharmaceutically acceptable carrier.
165 . A method for the treatment or prophylaxis of Yellow Fever Virus infection comprising administering to a host an antivirally effective amount of the nucleoside of claim 133 or its pharmaceutically acceptable salt optionally in a pharmaceutically acceptable carrier.
166 . A method for the treatment or prophylaxis of Yellow Fever Virus infection comprising administering to a host an antivirally effective amount of a (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside (β-D) or its pharmaceutically acceptable salt thereof of the formula:
wherein
R 1 and R 7 are independently H, phosphate, including monophosphate, diphosphate, triphosphate, or a stabilized phosphate prodrug, H-phosphonate, including stabilized H-phosphonates, acyl, including optionally substituted phenyl and lower acyl, alkyl, including lower allyl, O-substituted carboxyalkylamino or its peptide derivatives, sulfonate ester, including alkyl or arylalkyl sulfonyl, including methanesulfonyl and benzyl, wherein the phenyl group is optionally substituted, a lipid, including a phospholipid, an L or D-amino acid (or racemic mixture), 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 1 or R 7 is independently H or phosphate; R 1 and R 7 can also be linked with cyclic phosphate group; and
R 6 is an optionally substituted alkyl (including lower allyl), cyano (CN), CH 3 , OCH 3 , OCH 2 CH 3 , hydroxy methyl (CH 2 OH), fluoromethyl (CH 2 F), azido (N 3 ), CHCN, CH 2 N 3 , CH 2 NH 2 , CH 2 NHCH 3 , CH 2 N(CH 3 ) 2 , alkyne (optionally substituted), or fluoro.
optionally in a pharmaceutically acceptable carrier.
167 . A method for the treatment or prophylaxis of Yellow Fever Virus infection comprising administering to a host an antivirally effective amount of a (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside (β-D) or its pharmaceutically acceptable salt thereof of the formula:
optionally in a pharmaceutically acceptable carrier.
168 . A method for the treatment or prophylaxis of Yellow Fever Virus infection comprising administering to a host an antivirally effective amount of a (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside (β-D) or its pharmaceutically acceptable salt thereof of the formula:
wherein
R 1 is H, phosphate, including monophosphate, diphosphate, triphosphate, or a stabilized phosphate prodrug, H-phosphonate, including stabilized H-phosphonates, acyl, including optionally substituted phenyl and lower acyl, alkyl, including lower alkyl, O-substituted Carboxyalkylamino or its peptide derivatives, sulfonate ester, including alkyl or arylalkyl sulfonyl, including methanesulfonyl and benzyl, wherein the phenyl group is optionally substituted, a lipid, including a phospholipid, an L or D-amino acid (or racemic mixture), 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 1 is H or phosphate.
optionally in a pharmaceutically acceptable carrier.
169 . A method for the treatment or prophylaxis of Yellow Fever Virus infection comprising administering to a host an antivirally effective amount of a (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside (β-D) or its pharmaceutically acceptable salt thereof of the formula:
optionally in a pharmaceutically acceptable carrier.
170 . A method for the treatment or prophylaxis of West Nile Virus infection comprising administering to a host an antivirally effective amount of the nucleoside of claim 130 or its pharmaceutically acceptable salt optionally in a pharmaceutically acceptable carrier.
171 . A method for the treatment or prophylaxis of West Nile Virus infection comprising administering to a host an antivirally effective amount of the nucleoside of claim 131 or its pharmaceutically acceptable salt optionally in a pharmaceutically acceptable carrier.
172 . A method for the treatment or prophylaxis of West Nile Virus infection comprising administering to a host an antivirally effective amount of the nucleoside of claim 132 or its pharmaceutically acceptable salt optionally in a pharmaceutically acceptable carrier.
173 . A method for the treatment or prophylaxis of West Nile Virus infection comprising administering to a host an antivirally effective amount of the nucleoside of claim 133 or its pharmaceutically acceptable salt optionally in a pharmaceutically acceptable carrier.
174 . A method for the treatment or prophylaxis of West Nile Virus infection comprising administering to a host an antivirally effective amount of a (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside (β-D) or its pharmaceutically acceptable salt thereof of the formula:
wherein
R 1 and R 7 are independently H, phosphates including monophosphate, diphosphate, triphosphate, or a stabilized phosphate prodrug, H-phosphonate, including stabilized H-phosphonates, acyl, including optionally substituted phenyl and lower acyl, alkyl, including lower alkyl, O-substituted carboxyalkylamino or its peptide derivatives, sulfonate ester, including alkyl or arylalkyl sulfonyl, including methanesulfonyl and benzyl, wherein the phenyl group is optionally substituted, a lipid, including a phospholipid, an L or D-amino acid (or racemic mixture), 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 1 or R 7 is independently H or phosphate; R 1 and R 7 can also be linked with cyclic phosphate group; and
R 6 is an optionally substituted alkyl (including lower alkyl), cyano (CN), CH 3 , OCH 3 , OCH 2 CH 3 , hydroxy methyl (CH 2 OH), fluoromethyl (CH 2 F), azido (N 3 ), CHCN, CH 2 N 3 , CH 2 NH 2 , CH 2 NHCH 3 , CH 2 N(CH 3 ) 2 , alkyne (optionally substituted), or fluoro.
optionally in a pharmaceutically acceptable carrier.
175 . A method for the treatment or prophylaxis of West Nile Virus infection comprising administering to a host an antivirally effective amount of a (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside (β-D) or its pharmaceutically acceptable salt thereof of the formula:
optionally in a pharmaceutically acceptable carrier.
176 . A method for the treatment or prophylaxis of West Nile Virus infection comprising administering to a host an antivirally effective amount of a (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside (β-D) or its pharmaceutically acceptable salt thereof of the formula:
wherein
R 1 is H, phosphate, including monophosphate, diphosphate, triphosphate, or a stabilized phosphate prodrug, H-phosphonate, including stabilized H-phosphonates, acyl, including optionally substituted phenyl and lower acyl, alkyl, including lower alkyl, O-substituted carboxyalkylamino or its peptide derivatives, sulfonate ester, including alkyl or arylalkyl sulfonyl, including methanesulfonyl and benzyl, wherein the phenyl group is optionally substituted, a lipid, including a phospholipid, an L or D-amino acid (or racemic mixture), 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 1 is H or phosphate.
optionally in a pharmaceutically acceptable carrier.
177 . A method for the treatment or prophylaxis of West Nile Virus infection comprising administering to a host an antivirally effective amount of a (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside (β-D) or its pharmaceutically acceptable salt thereof of the formula:
optionally in a pharmaceutically acceptable carrier.
178 . A method for the treatment or prophylaxis of Dengue Virus infection comprising administering to a host an antivirally effective amount of the nucleoside of claim 130 or its pharmaceutically acceptable salt optionally in a pharmaceutically acceptable carrier.
179 . A method for the treatment or prophylaxis of Dengue Virus infection comprising administering to a host an antivirally effective amount of the nucleoside of claim 131 or its pharmaceutically acceptable salt optionally in a pharmaceutically acceptable carrier.
180 . A method for the treatment or prophylaxis of Dengue Virus infection comprising administering to a host an antivirally effective amount of the nucleoside of claim 132 or its pharmaceutically acceptable salt optionally in a pharmaceutically acceptable carrier.
181 . A method for the treatment or prophylaxis of Dengue Virus infection comprising administering to a host an antivirally effective amount of the nucleoside of claim 133 or its pharmaceutically acceptable salt optionally in a pharmaceutically acceptable carrier.
182 . A method for the treatment or prophylaxis of Dengue Virus infection comprising administering to a host an antivirally effective amount of a (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside (β-D) or its pharmaceutically acceptable salt thereof of the formula:
wherein
R 1 and R 7 are independently H, phosphate, including monophosphate, diphosphate, triphosphate, or a stabilized phosphate prodrug, H-phosphonate, including stabilized H-phosphonates, acyl, including optionally substituted phenyl and lower acyl, alkyl, including lower alkyl, O-substituted carboxyalkylamino or its peptide derivatives, sulfonate ester, including allyl or arylalkyl sulfonyl, including methanesulfonyl and benzyl, wherein the phenyl group is optionally substituted, a lipid, including a phospholipid, an L or D-amino acid (or racemic mixture), 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 1 or R 7 is independently H or phosphate; R 1 and R 7 can also be linked with cyclic phosphate group; and
R 6 is an optionally substituted alkyl (including lower allyl), cyano (CN), CH 3 , OCH 3 , OCH 2 CH 3 , hydroxy methyl (CH 2 OH), fluoromethyl (CH 2 F), azido (N 3 ), CHCN, CH 2 N 3 , CH 2 NH 2 , CH 2 NHCH 3 , CH 2 N(CH 3 ) 2 , alkyne (optionally substituted), or fluoro.
optionally in a pharmaceutically acceptable carrier.
183 . A method for the treatment or prophylaxis of Dengue Virus infection comprising administering to a host an antivirally effective amount of a (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside (β-D) or its pharmaceutically acceptable salt thereof of the formula:
optionally in a pharmaceutically acceptable carrier.
184 . A method for the treatment or prophylaxis of Dengue Virus infection comprising administering to a host an antivirally effective amount of a (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside (β-D) or its pharmaceutically acceptable salt thereof of the formula:
wherein
R 1 is H, phosphate, including monophosphate, diphosphate, triphosphate, or a stabilized phosphate prodrug, H-phosphonate, including stabilized H-phosphonates, acyl, including optionally substituted phenyl and lower acyl, alkyl, including lower alkyl, O-substituted carboxyalkylamino or its peptide derivatives, sulfonate ester, including alkyl or arylalkyl sulfonyl, including methanesulfonyl and benzyl, wherein the phenyl group is optionally substituted, a lipid, including a phospholipid, an L or D-amino acid (or racemic mixture), 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 1 is H or phosphate.
optionally in a pharmaceutically acceptable carrier.
185 . A method for the treatment or prophylaxis of Dengue Virus infection comprising administering to a host an antivirally effective amount of a (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside (β-D) or its pharmaceutically acceptable salt thereof of the formula:
optionally in a pharmaceutically acceptable carrier.
186 . The method of claim 146 , wherein the antivirally effective amount of (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside is administered in combination or alternation with at least one treatment selected from the group consisting of: interferon, including interferon alpah 2a, interferon alpha 2b, a pegylated interferon, interferon beta, interferon gamma, interferon tau and interferon omega; an interleukin, including interleukin 10 and interleukin 12; ribavirin; interferon alpha or pegylated interferon alpha in combination with ribavirin or levovirin; levovirin; a protease inhibitor including NS3 inhibitor, a NS3-4A inhibitor; a helicase inhibitor; a polymerase inhibitor including HCV RNA polymerase and NS5B polymerase inhibitor; gliotoxin; an IRES inhibitor, and antisense oligonucleotide; a thiazolidine derivative; a benzanilide, a ribozyme; another nucleoside, nucleoside prodrug or nucleoside derivative; a 1-amino-alkylcyclohexane; an antioxidant including vitamin E; squalene; amantadine; a bile acid; N-(phosphonoacetyl)-L-aspartic acid; a benzenedicarboxamide; polyadenylic acid; a benzimidazole; thymosin; a beta tubulin inhibitor; a prophylactic vaccine; an immune modulator, an IMPDH inhibitor; silybin-phosphatidylcholine phytosome; and mycophenolate.
187 . The method of claim 151 , wherein the antivirally effective amount of (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside is administered in combination or alternation with at least one treatment selected from the group consisting of: interferon, including interferon alpah 2a, interferon alpha 2b, a pegylated interferon, interferon beta, interferon gamma, interferon tau and interferon omega; an interleukin, including interleukin 10 and interleukin 12; ribavirin; interferon alpha or pegylated interferon alpha in combination with ribavirin or levovirin; levovirin; a protease inhibitor including NS3 inhibitor, a NS3-4A inhibitor; a helicase inhibitor; a polymerase inhibitor including HCV RNA polymerase and NS5B polymerase inhibitor; gliotoxin; an IRES inhibitor, and antisense oligonucleotide; a thiazolidine derivative; a benzanilide, a ribozyme; another nucleoside, nucleoside prodrug or nucleoside derivative; a 1-amino-alkylcyclohexane; an antioxidant including vitamin E; squalene; amantadine; a bile acid; N-(phosphonoacetyl)-L-aspartic acid; a benzenedicarboxamide; polyadenylic acid; a benzimidazole; thymosin; a beta tubulin inhibitor; a prophylactic vaccine; an immune modulator, an IMPDH inhibitor; silybin-phosphatidylcholine phytosome; and mycophenolate.
188 . The method of claim 153 , wherein the antivirally effective amount of (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside is administered in combination or alternation with at least one treatment selected from the group consisting of: interferon, including interferon alpah 2a, interferon alpha 2b, a pegylated interferon, interferon beta, interferon gamma, interferon tau and interferon omega; an interleukin, including interleukin 10 and interleukin 12; ribavirin; interferon alpha or pegylated interferon alpha in combination with ribavirin or levovirin; levovirin; a protease inhibitor including NS3 inhibitor, a NS3-4A inhibitor; a helicase inhibitor; a polymerase inhibitor including HCV RNA polymerase and NS5B polymerase inhibitor; gliotoxin; an IRES inhibitor, and antisense oligonucleotide; a thiazolidine derivative; a benzanilide, a ribozyme; another nucleoside, nucleoside prodrug or nucleoside derivative; a 1-amino-alkylcyclohexane; an antioxidant including vitamin E; squalene; amantadine; a bile acid; N-(phosphonoacetyl)-L-aspartic acid; a benzenedicarboxamide; polyadenylic acid; a benzimidazole; thymosin; a beta tubulin inhibitor; a prophylactic vaccine; an immune modulator, an IMPDH inhibitor; silybin-phosphatidylcholine phytosome; and mycophenolate.
189 . The method of claim 154 , wherein the antivirally effective amount of (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside is administered in combination or alternation with at least one treatment selected from the group consisting of: interferon, including interferon alpah 2a, interferon alpha 2b, a pegylated interferon, interferon beta, interferon gamma, interferon tau and interferon omega; an interleukin, including interleukin 10 and interleukin 12; ribavirin; interferon alpha or pegylated interferon alpha in combination with ribavirin or levovirin; levovirin; a protease inhibitor including NS3 inhibitor, a NS3-4A inhibitor; a helicase inhibitor; a polymerase inhibitor including HCV RNA polymerase and NS5B polymerase inhibitor; gliotoxin; an IRES inhibitor, and antisense oligonucleotide; a thiazolidine derivative; a benzanilide, a ribozyme; another nucleoside, nucleoside prodrug or nucleoside derivative; a 1-amino-alkylcyclohexane; an antioxidant including vitamin E; squalene; amantadine; a bile acid; N-(phosphonoacetyl)-L-aspartic acid; a benzenedicarboxamide; polyadenylic acid; a benzimidazole; thymosin; a beta tubulin inhibitor; a prophylactic vaccine; an immune modulator, an IMPDH inhibitor; silybin-phosphatidylcholine phytosome; and mycophenolate.
190 . The method of claim 159 , wherein the antivirally effective amount of (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside is administered in combination or alternation with at least one treatment selected from the group consisting of: interferon, including interferon alpah 2a, interferon alpha 2b, a pegylated interferon, interferon beta, interferon gamma, interferon tau and interferon omega; an interleukin, including interleukin 10 and interleukin 12; ribavirin; interferon alpha or pegylated interferon alpha in combination with ribavirin or levovirin; levovirin; a protease inhibitor including NS3 inhibitor, a NS3-4A inhibitor; a helicase inhibitor; a polymerase inhibitor including HCV RNA polymerase and NS5B polymerase inhibitor; gliotoxin; an IRES inhibitor, and antisense oligonucleotide; a thiazolidine derivative; a benzanilide, a ribozyme; another nucleoside, nucleoside prodrug or nucleoside derivative; a 1-amino-alkylcyclohexane; an antioxidant including vitamin E; squalene; amantadine; a bile acid; N-(phosphonoacetyl)-L-aspartic acid; a benzenedicarboxamide; polyadenylic acid; a benzimidazole; thymosin; a beta tubulin inhibitor; a prophylactic vaccine; an immune modulator, an IMPDH inhibitor; silybin-phosphatidylcholine phytosome; and mycophenolate.
191 . The method of claim 161 , wherein the antivirally effective amount of (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside is administered in combination or alternation with at least one treatment selected from the group consisting of: interferon, including interferon alpah 2a, interferon alpha 2b, a pegylated interferon, interferon beta, interferon gamma, interferon tau and interferon omega; an interleukin, including interleukin 10 and interleukin 12; ribavirin; interferon alpha or pegylated interferon alpha in combination with ribavirin or levovirin; levovirin; a protease inhibitor including NS3 inhibitor, a NS3-4A inhibitor; a helicase inhibitor; a polymerase inhibitor including HCV RNA polymerase and NS5B polymerase inhibitor; gliotoxin; an IRES inhibitor, and antisense oligonucleotide; a thiazolidine derivative; a benzanilide, a ribozyme; another nucleoside, nucleoside prodrug or nucleoside derivative; a 1-amino-alkylcyclohexane; an antioxidant including vitamin E; squalene; amantadine; a bile acid; N-(phosphonoacetyl)-L-aspartic acid; a benzenedicarboxamide; polyadenylic acid; a benzimidazole; thymosin; a beta tubulin inhibitor; a prophylactic vaccine; an immune modulator, an IMPDH inhibitor; silybin-phosphatidylcholine phytosome; and mycophenolate.
192 . The method of claim 162 , wherein the antivirally effective amount of (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside is administered in combination or alternation with at least one treatment selected from the group consisting of: interferon, including interferon alpah 2a, interferon alpha 2b, a pegylated interferon, interferon beta, interferon gamma, interferon tau and interferon omega; an interleukin, including interleukin 10 and interleukin 12; ribavirin; interferon alpha or pegylated interferon alpha in combination with ribavirin or levovirin; levovirin; a protease inhibitor including NS3 inhibitor, a NS3-4A inhibitor; a helicase inhibitor; a polymerase inhibitor including HCV RNA polymerase and NS5B polymerase inhibitor; gliotoxin; an IRES inhibitor, and antisense oligonucleotide; a thiazolidine derivative; a benzanilide, a ribozyme; another nucleoside, nucleoside prodrug or nucleoside derivative; a 1-amino-alkylcyclohexane; an antioxidant including vitamin E; squalene; amantadine; a bile acid; N-(phosphonoacetyl)-L-aspartic acid; a benzenedicarboxamide; polyadenylic acid; a benzimidazole; thymosin; a beta tubulin inhibitor; a prophylactic vaccine; an immune modulator, an IMPDH inhibitor; silybin-phosphatidylcholine phytosome; and mycophenolate.
193 . The method of claim 167 , wherein the antivirally effective amount of (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside is administered in combination or alternation with at least one treatment selected from the group consisting of: interferon, including interferon alpah 2a, interferon alpha 2b, a pegylated interferon, interferon beta, interferon gamma, interferon tau and interferon omega; an interleukin, including interleukin 10 and interleukin 12; ribavirin; interferon alpha or pegylated interferon alpha in combination with ribavirin or levovirin; levovirin; a protease inhibitor including NS3 inhibitor, a NS3-4A inhibitor; a helicase inhibitor; a polymerase inhibitor including HCV RNA polymerase and NS5B polymerase inhibitor; gliotoxin; an IRES inhibitor, and antisense oligonucleotide; a thiazolidine derivative; a benzanilide, a ribozyme; another nucleoside, nucleoside prodrug or nucleoside derivative; a 1-amino-alkylcyclohexane; an antioxidant including vitamin E; squalene; amantadine; a bile acid; N-(phosphonoacetyl)-L-aspartic acid; a benzenedicarboxamide; polyadenylic acid; a benzimidazole; thymosin; a beta tubulin inhibitor; a prophylactic vaccine; an immune modulator, an IMPDH inhibitor; silybin-phosphatidylcholine phytosome; and mycophenolate.
194 . The method of claim 169 , wherein the antivirally effective amount of (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside is administered in combination or alternation with at least one treatment selected from the group consisting of: interferon, including interferon alpah 2a, interferon alpha 2b, a pegylated interferon, interferon beta, interferon gamma, interferon tau and interferon omega; an interleukin, including interleukin 10 and interleukin 12; ribavirin; interferon alpha or pegylated interferon alpha in combination with ribavirin or levovirin; levovirin; a protease inhibitor including NS3 inhibitor, a NS3-4A inhibitor; a helicase inhibitor; a polymerase inhibitor including HCV RNA polymerase and NS5B polymerase inhibitor; gliotoxin; an IRES inhibitor, and antisense oligonucleotide; a thiazolidine derivative; a benzanilide, a ribozyme; another nucleoside, nucleoside prodrug or nucleoside derivative; a 1-amino-alkylcyclohexane; an antioxidant including vitamin E; squalene; amantadine; a bile acid; N-(phosphonoacetyl)-L-aspartic acid; a benzenedicarboxamide; polyadenylic acid; a benzimidazole; thymosin; a beta tubulin inhibitor; a prophylactic vaccine; an immune modulator, an IMPDH inhibitor; silybin-phosphatidylcholine phytosome; and mycophenolate.
195 . The method of claim 170 , wherein the antivirally effective amount of (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside is administered in combination or alternation with at least one treatment selected from the group consisting of: interferon, including interferon alpah 2a, interferon alpha 2b, a pegylated interferon, interferon beta, interferon gamma, interferon tau and interferon omega; an interleukin, including interleukin 10 and interleukin 12; ribavirin; interferon alpha or pegylated interferon alpha in combination with ribavirin or levovirin; levovirin; a protease inhibitor including NS3 inhibitor, a NS3-4A inhibitor; a helicase inhibitor; a polymerase inhibitor including HCV RNA polymerase and NS5B polymerase inhibitor; gliotoxin; an IRES inhibitor, and antisense oligonucleotide; a thiazolidine derivative; a benzanilide, a ribozyme; another nucleoside, nucleoside prodrug or nucleoside derivative; a 1-amino-alkylcyclohexane; an antioxidant including vitamin E; squalene; amantadine; a bile acid; N-(phosphonoacetyl)-L-aspartic acid; a benzenedicarboxamide; polyadenylic acid; a benzimidazole; thymosin; a beta tubulin inhibitor; a prophylactic vaccine; an immune modulator, an IMPDH inhibitor; silybin-phosphatidylcholine phytosome; and mycophenolate.
196 . The method of claim 175 , wherein the antivirally effective amount of (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside is administered in combination or alternation with at least one treatment selected from the group consisting of: interferon, including interferon alpah 2a, interferon alpha 2b, a pegylated interferon, interferon beta, interferon gamma, interferon tau and interferon omega; an interleukin, including interleukin 10 and interleukin 12; ribavirin; interferon alpha or pegylated interferon alpha in combination with ribavirin or levovirin; levovirin; a protease inhibitor including NS3 inhibitor, a NS3-4A inhibitor; a helicase inhibitor; a polymerase inhibitor including HCV RNA polymerase and NS5B polymerase inhibitor; gliotoxin; an IRES inhibitor, and antisense oligonucleotide; a thiazolidine derivative; a benzanilide, a ribozyme; another nucleoside, nucleoside prodrug or nucleoside derivative; a 1-amino-alkylcyclohexane; an antioxidant including vitamin E; squalene; amantadine; a bile acid; N-(phosphonoacetyl)-L-aspartic acid; a benzenedicarboxamide; polyadenylic acid; a benzimidazole; thymosin; a beta tubulin inhibitor; a prophylactic vaccine; an immune modulator, an IMPDH inhibitor; silybin-phosphatidylcholine phytosome; and mycophenolate.
197 . The method of claim 177 , wherein the antivirally effective amount of (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside is administered in combination or alternation with at least one treatment selected from the group consisting of: interferon, including interferon alpah 2a, interferon alpha 2b, a pegylated interferon, interferon beta, interferon gamma, interferon tau and interferon omega; an interleukin, including interleukin 10 and interleukin 12; ribavirin; interferon alpha or pegylated interferon alpha in combination with ribavirin or levovirin; levovirin; a protease inhibitor including NS3 inhibitor, a NS3-4A inhibitor; a helicase inhibitor; a polymerase inhibitor including HCV RNA polymerase and NS5B polymerase inhibitor; gliotoxin; an IRES inhibitor, and antisense oligonucleotide; a thiazolidine derivative; a benzanilide, a ribozyme; another nucleoside, nucleoside prodrug or nucleoside derivative; a 1-amino-alkylcyclohexane; an antioxidant including vitamin E; squalene; amantadine; a bile acid; N-(phosphonoacetyl)-L-aspartic acid; a benzenedicarboxamide; polyadenylic acid; a benzimidazole; thymosin; a beta tubulin inhibitor; a prophylactic vaccine; an immune modulator, an IMPDH inhibitor; silybin-phosphatidylcholine phytosome; and mycophenolate.
198 . The method of claim 178 , wherein the antivirally effective amount of (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside is administered in combination or alternation with at least one treatment selected from the group consisting of: interferon, including interferon alpah 2a, interferon alpha 2b, a pegylated interferon, interferon beta, interferon gamma, interferon tau and interferon omega; an interleukin, including interleukin 10 and interleukin 12; ribavirin; interferon alpha or pegylated interferon alpha in combination with ribavirin or levovirin; levovirin; a protease inhibitor including NS3 inhibitor, a NS3-4A inhibitor; a helicase inhibitor; a polymerase inhibitor including HCV RNA polymerase and NS5B polymerase inhibitor; gliotoxin; an IRES inhibitor, and antisense oligonucleotide; a thiazolidine derivative; a benzanilide, a ribozyme; another nucleoside, nucleoside prodrug or nucleoside derivative; a 1-amino-alkylcyclohexane; an antioxidant including vitamin E; squalene; amantadine; a bile acid; N-(phosphonoacetyl)-L-aspartic acid; a benzenedicarboxamide; polyadenylic acid; a benzimidazole; thymosin; a beta tubulin inhibitor; a prophylactic vaccine; an immune modulator, an IMPDH inhibitor; silybin-phosphatidylcholine phytosome; and mycophenolate.
199 . The method of claim 183 , wherein the antivirally effective amount of (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside is administered in combination or alternation with at least one treatment selected from the group consisting of: interferon, including interferon alpah 2a, interferon alpha 2b, a pegylated interferon, interferon beta, interferon gamma, interferon tau and interferon omega; an interleukin, including interleukin 10 and interleukin 12; ribavirin; interferon alpha or pegylated interferon alpha in combination with ribavirin or levovirin; levovirin; a protease inhibitor including NS3 inhibitor, a NS3-4A inhibitor; a helicase inhibitor; a polymerase inhibitor including HCV RNA polymerase and NS5B polymerase inhibitor; gliotoxin; an IRES inhibitor, and antisense oligonucleotide; a thiazolidine derivative; a benzanilide, a ribozyme; another nucleoside, nucleoside prodrug or nucleoside derivative; a 1-amino-alkylcyclohexane; an antioxidant including vitamin E; squalene; amantadine; a bile acid; N-(phosphonoacetyl)-L-aspartic acid; a benzenedicarboxamide; polyadenylic acid; a benzimidazole; thymosin; a beta tubulin inhibitor; a prophylactic vaccine; an immune modulator, an IMPDH inhibitor; silybin-phosphatidylcholine phytosome; and mycophenolate.
200 . The method of claim 185 , wherein the antivirally effective amount of (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside is administered in combination or alternation with at least one treatment selected from the group consisting of: interferon, including interferon alpah 2a, interferon alpha 2b, a pegylated interferon, interferon beta, interferon gamma, interferon tau and interferon omega; an interleukin, including interleukin 10 and interleukin 12; ribavirin; interferon alpha or pegylated interferon alpha in combination with ribavirin or levovirin; levovirin; a protease inhibitor including NS3 inhibitor, a NS3-4A inhibitor; a helicase inhibitor; a polymerase inhibitor including HCV RNA polymerase and NS5B polymerase inhibitor; gliotoxin; an IRES inhibitor, and antisense oligonucleotide; a thiazolidine derivative; a benzanilide, a ribozyme; another nucleoside, nucleoside prodrug or nucleoside derivative; a 1-amino-alkylcyclohexane; an antioxidant including vitamin E; squalene; amantadine; a bile acid; N-(phosphonoacetyl)-L-aspartic acid; a benzenedicarboxamide; polyadenylic acid; a benzimidazole; thymosin; a beta tubulin inhibitor; a prophylactic vaccine; an immune modulator, an IMPDH inhibitor; silybin-phosphatidylcholine phytosome; and mycophenolate.