Optimization of Pharmacokinetics through Manipulation of Physicochemical Properties in a Series of HCV Inhibitors
ACS Medicinal Chemistry Letters2011Vol. 2(10), pp. 715–719
Citations Over TimeTop 24% of 2011 papers
Scott E. Lazerwith, Gina Bahador, Eda Canales, Guofeng Cheng, Lee S. Chong, Michael O. Clarke, Edward Doerffler, Eugene Eisenberg, Jaclyn Hayes, Bing Lu, Qi Liu, Mike Matles, Michael Mertzman, Michael L. Mitchell, Philip Morganelli, Bernard P. Murray, Margaret Robinson, Robert G. Strickley, Megan Tessler, Neeraj Tirunagari, Jianhong Wang, Yujin Wang, Jennifer R. Zhang, Xubin Zheng, Weidong Zhong, William J. Watkins
Abstract
A novel series of HCV replication inhibitors based on a pyrido[3,2-d]pyrimidine 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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