Structure-activity relationships of 4-hydroxy-4-biaryl-proline acylsulfonamide tripeptides: A series of potent NS3 protease inhibitors for the treatment of hepatitis C virus

[Display omitted] The design and synthesis of a series of tripeptide acylsulfonamides as potent inhibitors of the HCV NS3/4A serine protease is described. These analogues house a C4 aryl, C4 hydroxy-proline at the S2 position of the tripeptide scaffold. Information relating to structure-activity rel...

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Veröffentlicht in:	Bioorganic & medicinal chemistry letters 2017-02, Vol.27 (3), p.590-596
Hauptverfasser:	Wang, Alan Xiangdong, Chen, Jie, Zhao, Qian, Sun, Li-Qiang, Friborg, Jacques, Yu, Fei, Hernandez, Dennis, Good, Andrew C., Klei, Herbert E., Rajamani, Ramkumar, Mosure, Kathy, Knipe, Jay O., Li, Danshi, Zhu, Jialong, Levesque, Paul C., McPhee, Fiona, Meanwell, Nicholas A., Scola, Paul M.
Format:	Artikel
Sprache:	eng
Schlagworte:	Animals Antiviral Agents - chemistry Antiviral Agents - pharmacokinetics Antiviral Agents - pharmacology C4 aryl, C4 hydroxy-proline Cardiovascular profiles Half-Life HCV NS3/4A serine protease inhibitors Heart - drug effects Hepacivirus - drug effects Hepacivirus - enzymology Humans In Vitro Techniques Oligopeptides - chemistry Oligopeptides - pharmacokinetics Oligopeptides - pharmacology Potent and orally bioavailable Proline - chemistry Protease Inhibitors - chemistry Protease Inhibitors - pharmacokinetics Protease Inhibitors - pharmacology Rabbits Rats Structure-Activity Relationship Sulfonamides - chemistry Tripeptide acylsulfonamides Viral Nonstructural Proteins - antagonists & inhibitors Viral Nonstructural Proteins - metabolism
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Zusammenfassung:	[Display omitted] The design and synthesis of a series of tripeptide acylsulfonamides as potent inhibitors of the HCV NS3/4A serine protease is described. These analogues house a C4 aryl, C4 hydroxy-proline at the S2 position of the tripeptide scaffold. Information relating to structure-activity relationships as well as the pharmacokinetic and cardiovascular profiles of these analogues is provided.
ISSN:	0960-894X 1464-3405
DOI:	10.1016/j.bmcl.2016.12.013