Substituted nucleosides, nucleotides and analogs thereof
AssigneeJanssen Pharmaceutica NV
InventorsLawrence M. Blatt, Leonid Beigelman, Natalia Dyatkina, Julian Alexander Symons, David Bernard Smith
Life of this patent
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Abstract
Disclosed herein are nucleosides, nucleotide analogs, methods of synthesizing nucleotide analogs and methods of treating diseases and/or conditions such as a Filoviridae virus infection with one or more nucleosides and/or nucleotide analogs.
Claims30
A method for ameliorating or treating a Filoviridae viral infection comprising contacting a cell infected with a Filoviridae virus with an effective amount of a compound of Formula (I), or a pharmaceutically acceptable salt thereof, wherein the compound of Formula (I) has the structure:
- wherein:
- B1A is
- R3A is selected from the group consisting of halogen, OH, and —OC(═O)R″A;
- R4A is selected from the group consisting of OH and halogen;
- Ra1 and Ra2 are independently hydrogen or deuterium;
- RA is hydrogen, deuterium, or cyano;
- R1A is selected from the group consisting of hydrogen,
- R2A is halogen or halogen(C1-6alkyl);
- R5A is selected from the group consisting of hydrogen, halogen, C1-6 alkyl and cyano;
- R6A and R7A are independently selected from the group consisting of absent, hydrogen, and
- or
- R6A is
- and R7A is absent or hydrogen;
- R8A is absent, hydrogen or aryl;
- R9A is N-alanine, N-valine, N-leucine, N-alanine isopropyl ester, N-alanine cyclohexyl ester, N-alanine neopentyl ester, N-valine isopropyl ester or N-leucine isopropyl ester;
- R10A and R11A are independently N-alanine, N-valine, N-leucine, N-alanine isopropyl ester, N-alanine cyclohexyl ester, N-alanine neopentyl ester, N-valine isopropyl ester or N-leucine isopropyl ester;
- R12A and R13A are independently absent or hydrogen;
- R14A is O− or OH;
- R22A and R23A are each hydrogen;
- R24A is selected from the group consisting of C1-24 alkyl and —O—C1-24 alkyl;
- and
- Z1A, Z2A, Z3A and Z4A are each O.
A method for inhibiting replication of Filoviridae viral infection comprising contacting a cell infected with a Filoviridae virus with an effective amount of a compound of Formula (I), or a pharmaceutically acceptable salt thereof, wherein the compound of Formula (I) has the structure:
- wherein:
- B1A is
- R3A is selected from the group consisting of halogen, OH, and —OC(═O)R″A;
- R4A is selected from the group consisting of OH and halogen;
- Ra1 and Ra2 are independently hydrogen or deuterium;
- RA is hydrogen, deuterium or cyano;
- R1A is selected from the group consisting of hydrogen,
- R2A is halogen or halogen(C1-6alkyl);
- R5A is selected from the group consisting of hydrogen, halogen, C1-6 alkyl and cyano;
- R6A and R7A are independently selected from the group consisting of absent, hydrogen, and
- or
- R6A is
- and R7A is absent or hydrogen;
- R8A is absent, hydrogen or aryl;
- R9A is N-alanine, N-valine, N-leucine, N-alanine isopropyl ester, N-alanine cyclohexyl ester, N-alanine neopentyl ester, N-valine isopropyl ester or N-leucine isopropyl ester;
- R10A and R11A are independently N-alanine, N-valine, N-leucine, N-alanine isopropyl ester, N-alanine cyclohexyl ester, N-alanine neopentyl ester, N-valine isopropyl ester or N-leucine isopropyl ester;
- R12A and R13A are independently absent or hydrogen;
- R14A is O− or OH;
- R22A and R23A are each hydrogen;
- R24A is selected from the group consisting of hydrogen, C1-24 alkyl, and —O—C1-24 alkyl;
- R″A is C1-24 alkyl;
- m is 0 or 1;
- s is 0, 1, 2 or 3;
- and
- Z1A, Z2A, Z3A and Z4A are each O.
Dependencies are inferred from the claim text.