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Retro-binding thrombin active site inhibitors: identification of an orally active inhibitor of thrombin catalytic activity. 2002
Edwin J Iwanowicz, and
S David Kimball, and
James Lin, and
Wan Lau, and
W-C Han, and
Tammy C Wang, and
Daniel G M Roberts, and
W A Schumacher, and
Martin L Ogletree, and
Steven M Seiler
Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543-4000, USA. iwanowie@bms.com
A series of retro-binding inhibitors of human alpha-thrombin was prepared to elucidate structure-activity relationships (SAR) and optimize in vivo performance. Compounds 9 and 11, orally active inhibitors of thrombin catalytic activity, were identified to be efficacious in a thrombin-induced lethality model in mice.
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