2′-fluoronucleoside phosphonates as antiviral agents

A compound having a structure consistent with formula (II) or a pharmaceutically acceptable salt thereof,

• wherein:
• a) X is O, S, SO2, or CH2;
• b) Z is O, S, or NH;
• c) R1 is H or CH3;
• d) R2 and R3 are independently a hydrogen, halogen, OH, OR′, SH, SR′, N3, NH2, NHR′, CN, OCOR′, OCOOR′, lower alkyl of C1-C6, halogenated lower alkyl of C1-C6, lower alkenyl of C2-C6, halogenated lower alkenyl of C2-C6, lower alkynyl of C2-C6, halogenated lower alkynyl of C2-C6, lower alkoxy of C1-C6, lower alkyl acid of C2-C6, or lower alkyl acid ester of C2-C6, wherein at least one of R2 and R3 is OH,
• e) R4 and R5 are independently a hydrogen, phosphate, diphosphate, or analogs thereof wherein one or two hydrogens on a P(OH) moiety is replaced with an C1-10 alkyl, aryl, amino acid ester, steroid, carbohydrate, or lipid group, wherein aryl groups are selected from the group consisting of phenyl, biphenyl, and naphthyl, optionally substituted with one or more moieties selected from the group consisting of hydroxyl, amino, alkylamino, arylamino, alkoxy, aryloxy, nitro, cyano, sulfonic acid, sulfate, phosphonic acid, phosphate, and phosphonate,
• f) Base is a heterocycle containing at least one nitrogen;
• and
• g) each R′ is independently a hydrogen, lower alkyl of C1-C6, or lower cycloalkyl of C1-C6.

A compound having a structure consistent with formula (III) or a pharmaceutically acceptable salt thereof,

• wherein:
• a) X is O, S, SO2, or CH2;
• b) n is 1 or 2;
• c) R4 and R5 are independently a hydrogen, phosphate, diphosphate, or analogs thereof wherein one or two hydrogens on a P(OH) moiety is replaced with an C1-10 alkyl, aryl, amino acid ester, steroid, carbohydrate, or lipid group, wherein aryl groups are selected from the group consisting of phenyl, biphenyl, and naphthyl, optionally substituted with one or more moieties selected from the group consisting of hydroxyl, amino, alkylamino, arylamino, alkoxy, aryloxy, nitro, cyano, sulfonic acid, sulfate, phosphonic acid, phosphate, and phosphonate;
• and
• d) Base is a heterocycle containing at least one nitrogen.

A compound having a structure consistent with formula (II) or a pharmaceutically acceptable salt thereof,

• wherein:
• a) X is O, S, SO2 , or CR2;
• b) Z is O, S, or NH;
• c) R1 is CH3,
• d) R2 and R3 are independently a hydrogen, halogen, OH, OR′, SH, SR′, N3, NH2, NHR′, CN, OCOR′, OCOOR′, lower alkyl of C1-C6, halogenated lower alkyl of C1-C6, lower alkenyl of C2-C6, halogenated lower alkenyl of C2-C6, lower alkynyl of C2-C6, halogenated lower alkynyl of C2-C6, lower alkoxy of C1-C6, lower alkyl acid of C2-C6, or lower alkyl acid ester of C2-C6,
• e) R4 and R5 are independently a hydrogen, phosphate, diphosphate, or analogs thereof wherein one or two hydrogens on a P(OH) moiety is replaced with an C1-10 alkyl, aryl, amino acid ester, steroid, carbohydrate, or lipid group, wherein aryl groups are selected from the group consisting of phenyl, biphenyl, and naphthyl, optionally substituted with one or more moieties selected from the group consisting of hydroxyl, amino, alkylamino, arylamino, alkoxy, aryloxy, nitro, cyano, sulfonic acid, sulfate, phosphonic acid, phosphate, and phosphonate;
• f) Base is a heterocycle containing at least one nitrogen;
• and g) each R′ is independently a hydrogen, lower alkyl of C1-C6, or lower cycloalkyl of C1-C6.

A compound having a structure consistent with formula (II) or a pharmaceutically acceptable salt thereof,

• wherein:
• a) X is O, S, SO2, or CH2;
• b) Z is O, S, or NH;
• c) R1 is H or CH3;
• d) R2 is selected from the group consisting of hydrogen, halogen, OH, OR′, SH, SR′, N3, NH2, NHR′, CN, OCOR′, OCOOR′, lower alkyl of C1-C6, halogenated lower alkyl of C1-C6, lower alkenyl of C2-C6, halogenated lower alkenyl of C2-C6, lower alkynyl of C2-C6, halogenated lower alkynyl of C2-C6, lower alkoxy of C1-C6, lower alkyl acid of C2-C6, and lower alkyl acid ester of C2-C6,
• e) R3 is selected from the group consisting of halogen, OR, OR′, SR, SR′, N3, NH2, NHR′, CN, OCOR′, OCOOR′, lower alkyl of C1-C6, halogenated lower alkyl of C1-C6, lower alkenyl of C2-C6, halogenated lower alkenyl of C2-C6, lower alkynyl of C2-C6, halogenated lower alkynyl of C2-C6, lower alkoxy of C1-C6, lower alkyl acid of C2-C6, and lower alkyl acid ester of C2-C6,
• f) R4 and R5 are independently a hydrogen, phosphate, diphosphate, or analogs thereof wherein one or two hydrogens on a P(OH) moiety is replaced with an C1-10 alkyl, aryl, amino acid ester, steroid, carbohydrate, or lipid group, wherein aryl groups are selected from the group consisting of phenyl, biphenyl, and naphthyl, optionally substituted with one or more moieties selected from the group consisting of hydroxyl, amino, alkylamino, arylamino, alkoxy, aryloxy, nitro, cyano, sulfonic acid, sulfate, phosphonic acid, phosphate, and phosphonate;
• g) Base is a heterocycle containing at least one nitrogen;
• and
• h) each R′ is independently a hydrogen, lower alkyl of C1-C6, or lower cycloalkyl of C1-C6.