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US 2014/0234253 A1Published application
Combination Treatments For Hepatitis C
AssigneeGlaxoSmithKline LLC
InventorsJill Walker, Christian Voitenleitner
Life of this patent
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Abstract
The present invention features methods and pharmaceutical compositions for the treatment of Hepatitis C in a human in need thereof comprising administering a compound of Formula (I), (II), (III), (IV), (V), or (VI) described herein or a pharmaceutically acceptable salt thereof in combination with one or more additional Hepatitis C therapeutic agents.
Claims31
A method of treating Hepatitis C in a human in need thereof comprising administering to the human a therapeutically effective amount of a compound of Formula (III):
- wherein:
- each R1 is independently H or C1-3alkyl;
- each R2 is independently C1-3alkyl;
- on each carbon to which there are R3 groups attached, either both R3s are H or the R3 groups together with the carbon to which they are bonded form a 4-, 5-, or 6-membered saturated spiro ring with the proviso that there is no more than 1 spiro ring on each saturated nitrogen-containing ring;
- each saturated spiro formed from R3 groups is independently cycloalkyl, or may contain 1 or 2 oxygen atoms, or 1 or 2 sulfur atoms, or 1 SO2, or 1 NR4;
- each R4 is independently H, C(O)OC1-4alkyl, C(O)C1-4alkyl, C(O)NC1-4alkyl, or SO2C1-4alkyl;
- and
- each spiro ring may optionally be substituted with deuterium, fluorine, or 1 or 2 methyl groups;
- or a pharmaceutically acceptable salt thereof,
- in combination with a one or more additional therapeutic agents selected from the group consisting of an HCV NS2 protease inhibitor, an HCV NS3/4A protease inhibitor, an HCV NS3 helicase inhibitor, an HCV NS4B replication factor inhibitor, an HCV NS5B polymerase inhibitor, an HCV entry inhibitor, an HCV internal ribosome entry site inhibitor, a microsomal triglyceride transfer protein inhibitor, an α-glucosidase inhibitor, a caspase inhibitor, a cyclophilin inhibitor, an immunomodulator, a metabolic pathway inhibitor, an interferon, and a nucleoside analogue.
7 more elements
A method of treatment of Hepatitis C Virus in a human in need thereof comprising administering a therapeutically effective amount of a compound of Formula (I):
- wherein:
- n is 2 or 3;
- each R1 is independently H or C1-3alkyl;
- each R2 is independently C1-3alkyl;
- each X is independently CRR, O, or S;
- and
- each R is independently methyl, hydrogen, or deuterium;
- or a pharmaceutically acceptable salt thereof, and one or more additional therapeutic agents selected from the group consisting of an HCV NS2 protease inhibitor, an HCV NS3/4A protease inhibitor, an HCV NS3 helicase inhibitor, an HCV NS4B replication factor inhibitor, an HCV NS5B polymerase inhibitor, an HCV entry inhibitor, an HCV internal ribosome entry site inhibitor, a microsomal triglyceride transfer protein inhibitor, an α-glucosidase inhibitor, a caspase inhibitor, a cyclophilin inhibitor, an immunomodulator, a metabolic pathway inhibitor, an interferon, and a nucleoside analogue.
5 more elements
A method of treatment of Hepatitis C Virus in a human in need thereof comprising administering a therapeutically effective amount of a compound of Formula (II):
- wherein:
- n is 2 or 3;
- each R1 is independently H or C1-3alkyl;
- each R2 is independently C1-3alkyl;
- each X is independently CRR, O, or S;
- and
- each R is independently methyl, hydrogen, or deuterium;
- or a pharmaceutically acceptable salt thereof, and one or more additional therapeutic agents selected from the group consisting of an HCV NS2 protease inhibitor, an HCV NS3/4A protease inhibitor, an HCV NS3 helicase inhibitor, an HCV NS4B replication factor inhibitor, an HCV NS5B polymerase inhibitor, an HCV entry inhibitor, an HCV internal ribosome entry site inhibitor, a microsomal triglyceride transfer protein inhibitor, an α-glucosidase inhibitor, a caspase inhibitor, a cyclophilin inhibitor, an immunomodulator, a metabolic pathway inhibitor, an interferon, and a nucleoside analogue.
5 more elements
A pharmaceutical composition comprising a compound of Formula (I):
- wherein:
- n is 2 or 3;
- each R1 is independently H or C1-3alkyl;
- each R2 is independently C1-3alkyl;
- each X is independently CRR, O, or S;
- and
- each R is independently methyl, hydrogen, or deuterium;
- or a pharmaceutically acceptable salt thereof, and one or more additional Hepatitis C therapeutic agents selected from the group consisting of an HCV NS2 protease inhibitor, an HCV NS3/4A protease inhibitor, an HCV NS3 helicase inhibitor, an HCV NS4B replication factor inhibitor, an HCV NS5B polymerase inhibitor, an HCV entry inhibitor, an HCV internal ribosome entry site inhibitor, a microsomal triglyceride transfer protein inhibitor, an α-glucosidase inhibitor, a caspase inhibitor, a cyclophilin inhibitor, an immunomodulator, a metabolic pathway inhibitor, an interferon, and a nucleoside analogue;
- and a pharmaceutically acceptable excipient.
6 more elements
A pharmaceutical composition comprising a compound of Formula (II):
- wherein:
- n is 2 or 3;
- each R1 is independently H or C1-3alkyl;
- each R2 is independently C1-3alkyl;
- each X is independently CRR, O, or S;
- and
- each R is independently methyl, hydrogen, or deuterium;
- or a pharmaceutically acceptable salt thereof, and one or more additional Hepatitis C therapeutic agents selected from the group consisting of an HCV NS2 protease inhibitor, an HCV NS3/4A protease inhibitor, an HCV NS3 helicase inhibitor, an HCV NS4B replication factor inhibitor, an HCV NS5B polymerase inhibitor, an HCV entry inhibitor, an HCV internal ribosome entry site inhibitor, a microsomal triglyceride transfer protein inhibitor, an α-glucosidase inhibitor, a caspase inhibitor, a cyclophilin inhibitor, an immunomodulator, a metabolic pathway inhibitor, an interferon, and a nucleoside analogue;
- and a pharmaceutically acceptable excipient.
6 more elements
A pharmaceutical composition comprising a compound of Formula (III):
- wherein:
- each R1 is independently H or C1-3alkyl;
- each R2 is independently C1-3alkyl;
- on each carbon to which there are R3 groups attached, either both R3s are H or the R3 groups together with the carbon to which they are bonded form a 4-, 5-, or 6-membered saturated spiro ring with the proviso that there is no more than 1 spiro ring on each saturated nitrogen-containing ring;
- each saturated spiro formed from R3 groups is independently cycloalkyl, or may contain 1 or 2 oxygen atoms, or 1 or 2 sulfur atoms, or 1 SO2, or 1 NR4;
- each R4 is independently H, C(O)OC1-4alkyl, C(O)C1-4alkyl, C(O)NC1-4alkyl, or SO2C1-4alkyl;
- and
- each spiro ring may optionally be substituted with deuterium, fluorine, or 1 or 2 methyl groups;
- or a pharmaceutically acceptable salt thereof, and one or more additional Hepatitis C therapeutic agents selected from the group consisting of an HCV NS2 protease inhibitor, an HCV NS3/4A protease inhibitor, an HCV NS3 helicase inhibitor, an HCV NS4B replication factor inhibitor, an HCV NS5B polymerase inhibitor, an HCV entry inhibitor, an HCV internal ribosome entry site inhibitor, a microsomal triglyceride transfer protein inhibitor, an α-glucosidase inhibitor, a caspase inhibitor, a cyclophilin inhibitor, an immunomodulator, a metabolic pathway inhibitor, an interferon, and a nucleoside analogue;
- and a pharmaceutically acceptable excipient.
7 more elements
A pharmaceutical composition comprising a compound having the structure:
- or a pharmaceutically acceptable salt thereof,
- in combination with a one or more additional Hepatitis C therapeutic agents selected from the group consisting of an HCV NS2 protease inhibitor, an HCV NS3/4A protease inhibitor, an HCV NS3 helicase inhibitor, an HCV NS4B replication factor inhibitor, an HCV NS5B polymerase inhibitor, an HCV entry inhibitor, an HCV internal ribosome entry site inhibitor, a microsomal triglyceride transfer protein inhibitor, an α-glucosidase inhibitor, a caspase inhibitor, a cyclophilin inhibitor, an immunomodulator, a metabolic pathway inhibitor, an interferon, and a nucleoside analogue;
- and a pharmaceutically acceptable excipient.
A pharmaceutical composition comprising a compound having the structure:
- or a pharmaceutically acceptable salt thereof,
- in combination with one or more compounds listed in Table 1;
- and a pharmaceutically acceptable excipient.
A pharmaceutical composition comprising a compound having the structure:
- or a pharmaceutically acceptable salt thereof,
- in combination with one or more compounds selected from the group of:
- Telaprevir
- Vertex
- Boceprevir
- Merck
- Vaniprevir (MK-7009)
- Merck
- MK-5172
- Merck
- Danoprevir (RG7227) (ITMN-191)
- Roche
- Simeprevir (TMC-435)
- JNJ Tibotec
- IDX-077
- Idenix
- IDX-791
- Idenix
- ACH-1625
- Achillion
- ACH-2684
- Achillion
- ABT-450
- Abbott
- VX-222
- Vertex
- Setrobuvir (RG-7790) (ANA-598)
- Roche
- TMC-647055
- J&J
- IDX-375
- Idenix
- ALS-2200
- Vertex
- ALS-2158
- Vertex
- Mericitabine (RG-7128)
- Roche
- IDX-184
- Idenix
- MK-4882
- Merck
- IDX-719
- Idenix
- IDX-19370
- Idenix
- IDX-19368
- Idenix
- ACH-2928
- Achillion
- ACH-3102
- Achillion
- PPI-461
- Presidio
- PPI-668
- Presidio
- PPI-437
- Presidio
- EDP-239
- Novartis
- MK-4882
- Merck
- GS-5885
- Gilead
- Daclatasvir (BMS-790052)
- BMS
- BMS-824393
- BMS
- ABT-267
- Abbott
- BI-201335
- BI
- BI-207127
- BI
- Filibuvir (PF-868554)
- Pfizer
- BMS-791325
- BMS
- INX-189
- BMS
- ABT-333
- Abbott
- ABT-072
- Abbott
- Debio-025
- Novartis
- SCY-635
- Scynexis
- Tegobuvir (GS-9190)
- Gilead
- GS-9669, and
- Gilead
- GS-7977
- Gilead;
- and a pharmaceutically
- acceptable excipient.
93 more elements
A pharmaceutical composition comprising a compound having the structure:
- or a pharmaceutically acceptable salt thereof,
- in combination with one or more compounds selected from the group of:
- Danoprevir (RG7227) (ITMN-191)
- Roche
- Simeprevir (TMC-435)
- JNJ Tibotec
- Setrobuvir (RG-7790) (ANA-598)
- Roche
- TMC-647055
- J&J
- Mericitabine (RG-7128)
- Roche
- GS-5885
- Gilead
- Tegobuvir (GS-9190)
- Gilead
- GS-9669, and
- Gilead
- GS-7977
- Gilead;
- and a pharmaceutically
- acceptable excipient.
19 more elements
A pharmaceutical composition comprising a compound having the structure:
- or a pharmaceutically acceptable salt thereof,
- in combination with one or more compounds selected from the group of:
- Danoprevir (RG7227) (ITMN-191)
- Roche
- Simeprevir (TMC-435)
- JNJ Tibotec
- Setrobuvir (RG-7790) (ANA-598)
- Roche
- TMC-647055, and
- J&J
- Mericitabine (RG-7128)
- Roche;
- and a pharmaceutically acceptable
- excipient.
11 more elements
A composition comprising a compound of Formula (IV):
- wherein each R is independently —CH(R1)—NH—C(O)—OR2;
- wherein each R1 is independently —CH(OH)—CH3 or —CH(OCH3)—CH3;
- and
- each R2 is independently C1-3alkyl;
- or a pharmaceutically acceptable salt thereof, in combination with one or more additional Hepatitis C therapeutic agents selected from the group consisting of an HCV NS2 protease inhibitor, an HCV NS3/4A protease inhibitor, an HCV NS3 helicase inhibitor, an HCV NS4B replication factor inhibitor, an HCV NS5B polymerase inhibitor, an HCV entry inhibitor, an HCV internal ribosome entry site inhibitor, a microsomal triglyceride transfer protein inhibitor, an α-glucosidase inhibitor, a caspase inhibitor, a cyclophilin inhibitor, an immunomodulator, a metabolic pathway inhibitor, an interferon, and a nucleoside analogue.
2 more elements
A method of preventing or treating Hepatitis C in a human in need thereof comprising administering to the human a compound of Formula (IV):
- wherein each R is independently —CH(R1)—NH—C(O)—OR2;
- wherein each R1 is independently —CH(OH)—CH3 or —CH(OCH3)—CH3;
- and
- each R2 is independently C1-3alkyl;
- or a pharmaceutically acceptable salt thereof, in combination with one or more additional Hepatitis C therapeutic agents selected from the group consisting of an HCV NS2 protease inhibitor, an HCV NS3/4A protease inhibitor, an HCV NS3 helicase inhibitor, an HCV NS4B replication factor inhibitor, an HCV NS5B polymerase inhibitor, an HCV entry inhibitor, an HCV internal ribosome entry site inhibitor, a microsomal triglyceride transfer protein inhibitor, an α-glucosidase inhibitor, a caspase inhibitor, a cyclophilin inhibitor, an immunomodulator, a metabolic pathway inhibitor, an interferon, and a nucleoside analogue.
2 more elements
A pharmaceutical composition comprising a compound of Formula (IV):
- wherein each R is independently —CH(R1)—NH—C(O)—OR2;
- wherein each R1 is independently —CH(OH)—CH3 or —CH(OCH3)—CH3;
- and
- each R2 is independently C1-3alkyl;
- or a pharmaceutically acceptable salt thereof, in combination with one or more additional Hepatitis C therapeutic agents selected from the group consisting of an HCV NS2 protease inhibitor, an HCV NS3/4A protease inhibitor, an HCV NS3 helicase inhibitor, an HCV NS4B replication factor inhibitor, an HCV NS5B polymerase inhibitor, an HCV entry inhibitor, an HCV internal ribosome entry site inhibitor, a microsomal triglyceride transfer protein inhibitor, an α-glucosidase inhibitor, a caspase inhibitor, a cyclophilin inhibitor, an immunomodulator, a metabolic pathway inhibitor, an interferon, and a nucleoside analogue,
- and a pharmaceutically acceptable carrier.
3 more elements
Dependencies are inferred from the claim text.