Development of a novel class of potent and selective FIXa inhibitors.

Using structure based drug design (SBDD), a novel class of potent coagulation Factor IXa (FIXa) inhibitors was designed and synthesized. High selectivity over FXa inhibition was achieved. Selected compounds demonstrated oral bioavailability in rat IV/PO pharmacokinetic (PK) studies. Finally, the pharmacodynamics (PD) of this class of molecules was evaluated in Thrombin Generation Assay (TGA) in Corn Trypsin Inhibitor (CTI) citrated human plasma and demonstrated characteristics of a FIXa inhibitor. Copyright © 2015 Elsevier Ltd. All rights reserved.

Citation

Ting Zhang, Patrick Andre, Thomas J Bateman, Yi-Heng Chen, Kunal Desai, Kenneth Ellsworth, Wayne M Geissler, Liangqin Guo, Alan Hruza, Tianying Jian, Dongfang Meng, Dann L Parker, Xiaoxia Qian, Paul Reichert, Edward C Sherer, Min Shu, Cameron J Smith, Lisa M Sonatore, Richard Tschirret-Guth, Andrew F Nolting, Robert Orr, Louis-Charles Campeau, Kazuto Araki, Teruyuki Nishimura, Isao Sakurada, Harold B Wood. Development of a novel class of potent and selective FIXa inhibitors. Bioorganic & medicinal chemistry letters. 2015 Nov 1;25(21):4945-9

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PMID: 25978966

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