NEW HAVEN, CT, United States
NEW HAVEN, CT, United States

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Patent
Achillion Pharmaceuticals, Inc. | Date: 2017-01-04

Compounds, methods of use, and processes for making inhibitors of complement factor D comprising Formula I, or a pharmaceutically acceptable salt or composition thereof are provided. The inhibitors described herein target factor D and inhibit or regulate the complement cascade at an early and essential point in the alternative complement pathway, and reduce factor Ds ability to modulate the classical and lectin complement pathways. The inhibitors of factor D described herein are capable of reducing the excessive activation of complement, which has been linked to certain autoimmune, inflammatory, and neurodegenerative diseases, as well as ischemia- reperfusion injury and cancer.


The present disclosure provides substituted aliphanes, cyclophanes, heteraphanes, heterophanes, hetero-heteraphanes and metallocenes, of Formula I D-M-D(Formula I) useful as antiviral agents. In certain embodiments disclosed herein M is a group -P-A-P- where A is Certain substituted aliphanes, cyclophanes, heteraphanes, heterophanes, hetero-heteraphanes and metallocenes disclosed herein are potent and/or selective inhibitors of viral replication, particularly Hepatitis C virus replication. Pharmaceutical compositions/and combinations containing one or more substituted aliphanes, cyclophanes, heteraphanes, heterophanes, hetero-heteraphanes and metallocenes and a pharmaceutically acceptable carrier are also provided by this disclosure. Methods for treating viral infections, including Hepatitis C viral infections are provided by the disclosure.


Patent
Achillion Pharmaceuticals, Inc. | Date: 2017-01-04

Compounds, methods of use, and processes for making inhibitors of complement factor D comprising Formula I, or a pharmaceutically acceptable salt or composition thereof, wherein R12 or R13 on the A group is an amide substituent (R32) are provided. The inhibitors described herein target factor D and inhibit or regulate the complement cascade at an early and essential point in the alternative complement pathway, and reduce factor Ds ability to modulate the classical and lectin complement pathways. The inhibitors of factor D described herein are capable of reducing the excessive activation of complement, which has been linked to certain autoimmune, inflammatory, and neurodegenerative diseases, as well as ischemia-reperfusion injury and cancer.


Patent
Achillion Pharmaceuticals, Inc. | Date: 2016-08-24

Provided is a compound having a structure selected from the group consisting of:N,N-[tricyclo[8.2.2.24,7]hexadeca-4,6,10,12,13,15-hexaene-5,11-diyl bis [1H-benzimidazole-6,2-diyl[(2S,3aS,7aS)-octahydro-1H-indole-2,1-diyl][(1S)-1-(1-methylethyl)-2-oxo-2,1-ethane diyl]]] bis-, C,C-dimethyl ester, which is a Hepatitis C virus NS5a (HCV NS5a) protease replication inhibitor


Patent
Achillion Pharmaceuticals, Inc. | Date: 2016-08-24

Compounds, methods of use, and processes for making inhibitors of complement factor D comprising Formula I, or a pharmaceutically acceptable salt or composition thereof are provided. The inhibitors described herein target factor D and inhibit or regulate the complement cascade. The inhibitors of factor D described herein are capable of reducing the excessive activation of complement.


Patent
Achillion Pharmaceuticals, Inc. | Date: 2016-08-24

Compounds, methods of use, and processes for making inhibitors of complement factor D comprising Formula I, or a pharmaceutically acceptable salt or composition thereof, wherein R^(12 )or R^(13 )on the A group is an amide substituent (R^(32)) are provided. The inhibitors described herein target factor D and inhibit or regulate the complement cascade in the alternative complement pathway. The inhibitors of factor D described herein reduce the excessive activation of complement.


Compounds, methods of use, and processes for making inhibitors of complement factor D comprising Formula I, or a pharmaceutically acceptable salt or composition thereof wherein R^(12 )or R^(13 )on the A group is an aryl, heteroaryl or heterocycle (R^(32)) are provided. The inhibitors described herein target factor D and inhibit or regulate the complement cascade. The inhibitors of factor D described herein reduce the excessive activation of complement.


Patent
Achillion Pharmaceuticals, Inc. | Date: 2016-08-24

Compounds, methods of use, and processes for making inhibitors of complement factor D comprising Formula I, or a pharmaceutically acceptable salt or composition thereof wherein R^(12 )or R^(13 )on the A group is a phosphonate (R^(32)) are provided. The inhibitors described herein target factor D and inhibit or regulate the complement cascade. The inhibitors of factor D described herein are capable of reducing the excessive activation of complement.


Patent
Achillion Pharmaceuticals, Inc. | Date: 2016-08-24

Compounds, methods of use, and processes for making inhibitors of complement factor D comprising Formula I, or a pharmaceutically acceptable salt or composition thereof wherein R^(12 )or R^(13 )on the A group is an ether (R^(32)) are provided. The inhibitors described herein target factor D and inhibit or regulate the complement cascade. The inhibitors of factor D described herein are capable of reducing the excessive activation of complement.


The present disclosure provides substituted aliphanes, cyclophanes, heteraphanes, heterophanes, hetero-heteraphanes and metallocenes, of Formula I D-M-D(Formula I) useful as antiviral agents. In certain embodiments disclosed herein M is a group P-A-P where A is Certain substituted aliphanes, cyclophanes, heteraphanes, heterophanes, hetero-heteraphanes and metallocenes disclosed herein are potent and/or selective inhibitors of viral replication, particularly Hepatitis C virus replication. Pharmaceutical compositions/and combinations containing one or more substituted aliphanes, cyclophanes, heteraphanes, heterophanes, hetero-heteraphanes and metallocenes and a pharmaceutically acceptable carrier are also provided by this disclosure. Methods for treating viral infections, including Hepatitis C viral infections are provided by the disclosure.

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