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1. A method for ameliorating, treating or preventing a norovirus infection comprising contacting a cell infected with the norovirus with an effective amount of a compound selected from Formula (I), Formula (II) and Formula (III), or a pharmaceutically acceptable salt of the foregoing, wherein Formula (I), Formula (II) and Formula (III) are: wherein: B1A, B1B and B1C are independently an optionally substituted heterocyclic base or an optionally substituted heterocyclic base with a protected amino group; Raa1 and Raa2 are independently hydrogen or deuterium; RA is hydrogen, deuterium, an unsubstituted C1-3 alkyl, an unsubstituted C2-4 alkenyl, an unsubstituted C2-3 alkynyl or cyano; R1A is selected from the group consisting of hydrogen, an optionally substituted acyl, an optionally substituted O-linked amino acid, R2A is selected from the group consisting of hydrogen, halogen, azido, an optionally substituted C1-6 alkyl, an optionally substituted C2-6 alkenyl, an optionally substituted C2-6 alkynyl, an optionally substituted C3-6 cycloalkyl, an optionally substituted —O—C1-6 alkyl, an optionally substituted —O—C3-6 alkenyl, an optionally substituted —O—C3-6 alkynyl and cyano; R3A is selected from the group consisting of halogen, OH, —OC(═O)R″A and an optionally substituted O-linked amino acid; R1B is selected from the group consisting of O−, OH, an optionally substituted C1-6alkoxy,an optionally substituted N-linked amino acid and an optionally substituted N-linked amino acid ester derivative;
R1C and R2C are independently selected from the group consisting of O−, OH, an optionally substituted C1-6 alkoxy,an optionally substituted N-linked amino acid and an optionally substituted N-linked amino acid ester derivative; or
R1C isand R2 is O− or OH;
R2B and R3C are independently selected from the group consisting of halogen, an optionally substituted C1-6 alkyl, an optionally substituted C2-6 alkenyl, an optionally substituted C2-6 alkynyl, an optionally substituted C3-6 cycloalkyl, an optionally substituted —O—C1-6 alkyl, an optionally substituted —O—C3-6 alkenyl, an optionally substituted —O—C3-6 alkynyl and cyano; R4C is selected from the group consisting of OH, —OC(═O)R″C and an optionally substituted O-linked amino acid; R4A, R3B and R5C are independently selected from the group consisting of hydrogen, halogen, OR1D, an optionally substituted O-linked amino acid, azido and NR2DR3D; R1D is hydrogen or —C(═O)R″D; R2D and R3D are independently hydrogen or an optionally substituted C1-6 alkyl; R5A, R4B and R6C are independently selected from the group consisting of hydrogen, halogen, an optionally substituted C1-6 alkyl, an optionally substituted C2-6 alkenyl and an optionally substituted C2-6 alkynyl; R6A, R7A and R8A are independently selected from the group consisting of absent, hydrogen, an optionally substituted C1-24 alkyl, an optionally substituted C2-24 alkenyl, an optionally substituted C2-24 alkynyl, an optionally substituted C3-6 cycloalkyl, an optionally substituted C3-6 cycloalkenyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted aryl(C1-6 alkyl), an optionally substituted *—(CR15AR16A)p—O—C1-24 alkyl, an optionally substituted *—(CR17AR18A)q—O—C1-24 alkenyl,or
R6A isand R7A is absent or hydrogen; or
R6A and R7A are taken together to form a moiety selected from the group consisting of an optionally substitutedand an optionally substitutedwherein the oxygens connected to R6A and R7A, the phosphorus and the moiety form a six-membered to ten-membered ring system;
R9A is independently selected from the group consisting of an optionally substituted C1-24 alkyl, an optionally substituted C2-24 alkenyl, an optionally substituted C2-24 alkynyl, an optionally substituted C3-6 cycloalkyl, an optionally substituted C3-6 cycloalkenyl, NR30AR31A, an optionally substituted N-linked amino acid and an optionally substituted N-linked amino acid ester derivative; R10A and R11A are independently an optionally substituted N-linked amino acid or an optionally substituted N-linked amino acid ester derivative; R12A, R13A and R14A are independently absent or hydrogen; each R15A, each R16A, each R17A and each R18A are independently hydrogen, an optionally substituted C1-24 alkyl or alkoxy; R19A, R20A, R22A, R23A, R5B, R6B, R8B, R9B, R9C, R10C, R12C and R13C are independently selected from the group consisting of hydrogen, an optionally substituted C1-24 alkyl and an optionally substituted aryl; R21A, R24A, R7B, R10B, R11C and R14C are independently selected from the group consisting of hydrogen, an optionally substituted C1-24 alkyl, an optionally substituted aryl, an optionally substituted —O—C1-24 alkyl, an optionally substituted —O-aryl, an optionally substituted —O-heteroaryl, an optionally substituted —O-monocyclic heterocyclyl and R25A1, R25A2, R29A, R11B1, R11B2, R15C1 and R15C2 are independently selected from the group consisting of hydrogen, an optionally substituted C1-24 alkyl and an optionally substituted aryl; R16C, R17C and R18C are independently absent or hydrogen; R26A and R27A are independently —C≡N or an optionally substituted substituent selected from the group consisting of C2-8 organylcarbonyl, C2-8 alkoxycarbonyl and C2-8 organylaminocarbonyl; R28A is selected from the group consisting of hydrogen, an optionally substituted C1-24-alkyl, an optionally substituted C2-24 alkenyl, an optionally substituted C2-24 alkynyl, an optionally substituted C3-6 cycloalkyl and an optionally substituted C3-6 cycloalkenyl; R30A and R31A are independently selected from the group consisting of hydrogen, an optionally substituted C1-24-alkyl, an optionally substituted C2-24 alkenyl, an optionally substituted C2-24 alkynyl, an optionally substituted C3-6 cycloalkyl and an optionally substituted C3-6 cycloalkenyl; for Formula (III), ------- is a single bond or a double bond;
when ------- is a single bond, each R7C and each R8C is independently hydrogen or halogen; andwhen ------- is a double bond, each R7C is absent and each R8C is independently hydrogen or halogen; R″A, R″C and R″D are independently an optionally substituted C1-24-alkyl; d, j and h are independently 1 or 2; e1, k1 and w1 are independently 0 or 1; e2, k2 and w2 are independently 3, 4 or 5; m and n are independently 0 or 1; p and q are independently selected from the group consisting of 1, 2 and 3; r is 1 or 2; Z1A, Z2A, Z3A, Z4A, Z1B, Z2B and Z1C are independently O or S; and provided that when R2A is hydrogen, then R5A is halogen, an optionally substituted C1-6 alkyl, an optionally substituted C2-6 alkenyl and an optionally substituted C2-6 alkynyl; and provided that the compound of Formula (I), or a pharmaceutically acceptable salt thereof, cannot be selected from the group consisting of 2′-C-methylcytidine, ribavirin, β-d-N4-hydroxycytidine, 2′-F-2′-methylcytidine, 2-thiouridine, 6-aza-uridine, 5-nitrocytidine and 2′-amino-2′-deoxycytidine, or a mono-, a di- or a tri-phosphate of the foregoing. |
