Discovery of an orally efficacious inhibitor of coagulation factor Xa which incorporates a neutral P1 ligand

YM Choi-Sledeski, R Kearney, G Poli…

文献索引：Choi-Sledeski, Yong Mi; Kearney, Robert; Poli, Gregory; Pauls, Henry; Gardner, Charles; Gong, Yong; Becker, Michael; Davis, Roderick; Spada, Alfred; Liang, Guyan; Chu, Valeria; Brown, Karen; Collussi, Dennis; Leadley Jr., Robert; Rebello, Sam; Moxey, Phillip; Morgan, Suzanne; Bentley, Ross; Kasiewski, Charles; Maignan, Sebastien; Guilloteau, Jean-Pierre; Mikol, Vincent Journal of Medicinal Chemistry, 2003 , vol. 46, # 5 p. 681 - 684

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被引用次数: 77

摘要

The discovery and SAR of ketopiperazino methylazaindole factor Xa inhibitors are described. Structure-activity data suggesting that this class of inhibitors does not bind in the canonical mode were confirmed by an X-ray crystal structure showing the neutral haloaromatic bound in the S1 subsite. The most potent azaindole, 33 (RPR209685), is selective against related serine proteases and attains higher levels of exposure upon oral ...