Discovery of Novel Thiophene-Based, Thumb Pocket 2 Allosteric Inhibitors of the Hepatitis C NS5B Polymerase with Improved Potency and Physicochemical Profiles

The hepatitis C viral proteins NS3/4A protease, NS5B polymerase, and NS5A are clinically validated targets for direct-acting antiviral therapies. The NS5B polymerase may be inhibited directly through the action of nucleosides or nucleotide analogues or allosterically at a number of well-defined site...

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Veröffentlicht in:	Journal of medicinal chemistry 2016-07, Vol.59 (13), p.6293-6302
Hauptverfasser:	Court, John J, Poisson, Carl, Ardzinski, Andrzej, Bilimoria, Darius, Chan, Laval, Chandupatla, Kishan, Chauret, Nathalie, Collier, Philip N, Das, Sanjoy Kumar, Denis, Francois, Dorsch, Warren, Iyer, Ganesh, Lauffer, David, L’Heureux, Lucille, Li, Pan, Luisi, Brian S, Mani, Nagraj, Nanthakumar, Suganthi, Nicolas, Olivier, Rao, B. Govinda, Ronkin, Steven, Selliah, Subajini, Shawgo, Rebecca S, Tang, Qing, Waal, Nathan D, Yannopoulos, Constantin G, Green, Jeremy
Format:	Artikel
Sprache:	eng
Schlagworte:	Allosteric Regulation - drug effects Antiviral Agents - chemical synthesis Antiviral Agents - chemistry Antiviral Agents - pharmacology Cyclohexanols - chemistry Cyclohexanols - pharmacology Dose-Response Relationship, Drug Drug Discovery Hepacivirus - drug effects Hepacivirus - enzymology Microbial Sensitivity Tests Models, Molecular Molecular Structure Structure-Activity Relationship Thiophenes - chemical synthesis Thiophenes - chemistry Thiophenes - pharmacology Viral Nonstructural Proteins - antagonists & inhibitors Viral Nonstructural Proteins - metabolism Virus Replication - drug effects
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