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dc.contributor.author McPhail, Andrew en_US
dc.date.accessioned 2011-06-21T17:26:37Z
dc.date.available 2011-06-21T17:26:37Z
dc.date.issued 2010 en_US
dc.identifier.citation Velazquez,Francisco;Sannigrahi,Mousumi;Bennett,Frank;Lovey,Raymond G.;Arasappan,Ashok;Bogen,Stephane;Nair,Latha;Venkatraman,Srikanth;Blackman,Melissa;Hendrata,Siska;Huang,Yuhua;Huelgas,Regina;Pinto,Patrick;Cheng,Kuo-Chi;Tong,Xiao;McPhail,Andrew T.;Njoroge,F. George. 2010. Cyclic Sulfones as Novel P3-Caps for Hepatitis C Virus NS3/4A (HCV NS3/4A) Protease Inhibitors: Synthesis and Evaluation of Inhibitors with Improved Potency and Pharmacokinetic Profiles. Journal of medicinal chemistry 53(8): 3075-3085. en_US
dc.identifier.issn 0022-2623 en_US
dc.identifier.uri http://hdl.handle.net/10161/4062
dc.description.abstract HCV infection affects more than 170 million people worldwide and many of those patients will reach the end stage complications of the disease which include hepatocarcinoma and liver failure. The success rate for treatment of patients infected with genotype-1 is about 40%. Therefore, novel treatments are needed to combat the infection. The HCV NS3 protease inhibitor Boceprevir (1) was reported by our research group and efforts continue for the discovery of more potent compounds with improved pharmacokinetic profiles. A new series of HCV NS3 protease inhibitors having a cyclic sulfone P3-cap have been discovered. Compounds 43 and 44 showed K-i* values in the single-digit nM range and their cellular potency was improved by 10-fold compared to 1. The pharmacokinetic profiles of 43 and 44 in rats and monkeys were also improved to achieve higher plasma levels after oral administration. en_US
dc.language.iso en_US en_US
dc.publisher AMER CHEMICAL SOC en_US
dc.relation.isversionof doi:10.1021/jm9016027 en_US
dc.subject serine-protease en_US
dc.subject discovery en_US
dc.subject replication en_US
dc.subject optimization en_US
dc.subject infection en_US
dc.subject ribavirin en_US
dc.subject imines en_US
dc.subject genome en_US
dc.subject p1 en_US
dc.subject chemistry, medicinal en_US
dc.title Cyclic Sulfones as Novel P3-Caps for Hepatitis C Virus NS3/4A (HCV NS3/4A) Protease Inhibitors: Synthesis and Evaluation of Inhibitors with Improved Potency and Pharmacokinetic Profiles en_US
dc.title.alternative en_US
dc.description.version Version of Record en_US
duke.date.pubdate 2010-4-22 en_US
duke.description.endpage 3085 en_US
duke.description.issue 8 en_US
duke.description.startpage 3075 en_US
duke.description.volume 53 en_US
dc.relation.journal Journal of medicinal chemistry en_US

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