Generation of potent coagulation protease inhibitors utilizing zinc-mediated chelation
Wendy B Young1, Paul Sprengeler, William D Shrader
1Celera, 180 Kimball Way, South San Francisco, CA 94080, USA. Wendy.Young@Celera.com
Bioorganic & Medicinal Chemistry Letters
|November 1, 2005
Abstract:
Inhibition of coagulation proteases such as thrombin, fXa, and fVIIa has been a focus of ongoing research to produce safe and effective antithrombotic agents. Herein, we describe a unique zinc-mediated chelation strategy to streamline the discovery of potent inhibitors of fIIa, fXa, and fVIIa. SAR studies that led to the development of selective inhibitors of fXa will also be detailed.
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