| 主权项 |
1. A method for ameliorating or treating a viral infection caused by a virus comprising administering to or contacting a cell in a subject 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 the virus is selected from a henipavirus, a morbillivirus, a respirovirus, a rubulavirus and a metapneumovirus, and wherein the compound is selected from Formula (I), Formula (II), and Formula (III) has one of the following structures: wherein: B1A B1B and B1C are independently an optionally substituted heterocyclic base or an optionally substituted heterocyclic base with a protected amino group; R1A is selected from the group consisting of hydrogen, an optionally substituted acyl, an optionally substituted O-linked amino acid, the dashed line (------)of Formula (I) is absent; R2A is selected from the group consisting of an unsubstituted C1-6 alkyl, a halogen substituted C1-6 alkyl, a hydroxy substituted C1-6 alkyl, an alkoloxy substituted C1-6 alkyl, a sulfenyl 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 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 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 is and R2C is O−or OH; R2B and R3 are independently selected from the group consisting of 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 a halogen; R5A, R4B and R6C are independently hydrogen or halogen; 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 is and R7A is absent or hydrogen; or R6A and R7A are taken together to form a moiety selected from the group consisting of an optionally substituted and an optionally substituted wherein 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, NR3OAR31A, 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 and an optionally substituted —O-aryl; R25A, R29A, R11B and R15C 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 and R″C are independently an optionally substituted C1-24-alkyl; 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 R1A is wherein R8A is an unsubstituted C1-4 alkyl or phenyl optionally para-substituted with a halogen or methyl and R9A is methyl ester, ethyl ester, isopropyl ester, n-butyl ester, benzyl ester or phenyl ester of an amino acid selected from the group consisting of glycine, alanine, valine, leucine, phenylalanine, tryptophan, methionine and proline; R3A is OH; R4A is fluoro; R5A is fluoro or hydrogen; and B1A is an unsubstituted uracil; then R2A cannot be —OCH3; provided that when R1A is H; R3A is OH; R4A is fluoro; R5A is fluoro; and B1A is an unsubstituted cytosine; then R2A cannot be allenyl; and provided that when R1A is H; R3A is OH; R4A is fluoro; R5A is fluoro; and B1A is an unsubstituted cytosine; then R2A cannot be ethynyl. |
