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Optimization of Pharmacokinetics through Manipulation of Physicochemical Properties in a Series of HCV Inhibitors

  作者 LAZERWITH SCOTT E; BAHADOR GINA; CANALES EDA; CHENG GUOFENG; CHONG LEE; CLARKE MICHAEL O; DOERFFLER EDWARD; EISENBERG EUGENE J; HAYES JACLYN; LU BING; LIU QI; MATLES MIKE; MERTZMAN MICHAEL; MITCHELL MICHAEL L; MORGANELLI PHILIP; MURRAY BERNARD P; ROBINSON MARGARET; STRICKLEY ROBERT G; TESSLER MEGAN; TIRUNAGARI NEERAJ; WANG JIANHONG; WANG YUJIN; ZHANG JENNIFER R; ZHENG XUBIN; ZHONG WEIDONG; WATKINS WILLIAM J  
  选自 期刊  ACS Medicinal Chemistry Letters;  卷期  2011年2-10;  页码  715-719  
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[摘要]A novel series of HCV replication inhibitors based on a pyrido[3,2-d]primidine core were optimized for pharmacokinetics (PK) in rats. Several associations between physicochemical properties and PK were identified and exploited to guide the design of compounds. In addition, a simple new metric that may aid in the prediction of bioavailability for compounds with higher polar surface area is described (3*HBD-cLogP).

 
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