| Literature DB >> 12570369 |
Christopher S Burgey1, Kyle A Robinson, Terry A Lyle, Philip E J Sanderson, S Dale Lewis, Bobby J Lucas, Julie A Krueger, Rominder Singh, Cynthia Miller-Stein, Rebecca B White, Bradley Wong, Elizabeth A Lyle, Peter D Williams, Craig A Coburn, Bruce D Dorsey, James C Barrow, Maria T Stranieri, Marie A Holahan, Gary R Sitko, Jacquelynn J Cook, Daniel R McMasters, Colleen M McDonough, William M Sanders, Audrey A Wallace, Franklin C Clayton, Dennis Bohn, Yvonne M Leonard, Theodore J Detwiler, Joseph J Lynch, Youwei Yan, Zhongguo Chen, Lawrence Kuo, Stephen J Gardell, Jules A Shafer, Joseph P Vacca.
Abstract
Recent efforts in the field of thrombin inhibitor research have focused on the identification of compounds with good oral bioavailability and pharmacokinetics. In this manuscript we describe a metabolism-based approach to the optimization of the 3-(2-phenethylamino)-6-methylpyrazinone acetamide template (e.g., 1) which resulted in the modification of each of the three principal components (i.e., P1, P2, P3) comprising this series. As a result of these studies, several potent thrombin inhibitors (e.g., 20, 24, 25) were identified which exhibit high levels of oral bioavailability and long plasma half-lives.Entities:
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Year: 2003 PMID： 12570369 DOI： 10.1021/jm020311f
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446