- DEUTERATED CFTR POTENTIATORS
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This invention relates to compounds of Formula (I):and pharmaceutically acceptable salts thereof, wherein each X and each R is defined within. This invention also provides compositions comprising a compound of this invention and the use of such compositions in methods of treating diseases and conditions that are beneficially treated by administering a CFTR potentiator.
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Paragraph 128
(2017/04/11)
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- Discovery of a novel series of potent non-nucleoside inhibitors of hepatitis C virus NS5B
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Hepatitis C virus (HCV) is a major global public health problem. While the current standard of care, a direct-acting antiviral (DAA) protease inhibitor taken in combination with pegylated interferon and ribavirin, represents a major advancement in recent years, an unmet medical need still exists for treatment modalities that improve upon both efficacy and tolerability. Toward those ends, much effort has continued to focus on the discovery of new DAAs, with the ultimate goal to provide interferon-free combinations. The RNA-dependent RNA polymerase enzyme NS5B represents one such DAA therapeutic target for inhibition that has attracted much interest over the past decade. Herein, we report the discovery and optimization of a novel series of inhibitors of HCV NS5B, through the use of structure-based design applied to a fragment-derived starting point. Issues of potency, pharmacokinetics, and early safety were addressed in order to provide a clinical candidate in fluoropyridone 19.
- Schoenfeld, Ryan C.,Bourdet, David L.,Brameld, Ken A.,Chin, Elbert,De Vicente, Javier,Fung, Amy,Harris, Seth F.,Lee, Eun K.,Le Pogam, Sophie,Leveque, Vincent,Li, Jim,Lui, Alfred S.-T.,Najera, Isabel,Rajyaguru, Sonal,Sangi, Michael,Steiner, Sandra,Talamas, Francisco X.,Taygerly, Joshua P.,Zhao, Junping
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supporting information
p. 8163 - 8182
(2013/11/06)
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- HETEROCYCLIC ANTIVIRAL COMPOUNDS
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Compounds having the formula I wherein wherein R1, R2, R3, R4, X1, X2, X3 and X4 and as defined herein are Hepatitis C virus NS5b polymerase inhibitors. Also disclosed are compositions and methods for treating an HCV infection and inhibiting HCV replication.
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Page/Page column 45
(2010/12/29)
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