473927-72-9Relevant academic research and scientific papers
Structure and property based design of factor Xa inhibitors: Biaryl pyrrolidin-2-ones incorporating basic heterocyclic motifs
Young, Robert J.,Borthwick, Alan D.,Brown, David,Burns-Kurtis, Cynthia L.,Campbell, Matthew,Chan, Chuen,Charbaut, Marie,Convery, Maire A.,Diallo, Hawa,Hortense, Eric,Irving, Wendy R.,Kelly, Henry A.,King, N. Paul,Kleanthous, Savvas,Mason, Andrew M.,Pateman, Anthony J.,Patikis, Angela N.,Pinto, Ivan L.,Pollard, Derek R.,Senger, Stefan,Shah, Gita P.,Toomey, John R.,Watson, Nigel S.,Weston, Helen E.,Zhou, Ping
, p. 28 - 33 (2008/09/17)
Structure and property based drug design was exploited in the synthesis of sulfonamidopyrrolidin-2-one-based factor Xa (fXa) inhibitors, incorporating basic biaryl P4 groups, producing highly potent inhibitors with significant anticoagulant activities and encouraging oral pharmacokinetic profiles.
Discovery of 1-(3′-aminobenzisoxazol-5′-yl)-3-trifluoromethyl- N-[2-fluoro-4-[(2′-dimethylaminomethyl)imidazol-1-yl]phenyl] -1H-pyrazole-5-carboxyamide hydrochloride (razaxaban), a highly potent, selective, and orally bioavailable factor Xa inhibitor
Quan, Mimi L.,Lam, Patrick Y. S.,Han, Qi,Pinto, Donald J. P.,He, Ming Y.,Li, Renhua,Ellis, Christopher D.,Clark, Charles G.,Teleha, Christopher A.,Sun, Jung-Hui,Alexander, Richard S.,Bai, Steve,Luettgen, Joseph M.,Knabb, Robert M.,Wong, Pancras C.,Wexler, Ruth R.
, p. 1729 - 1744 (2007/10/03)
Modification of a series of pyrazole factor Xa inhibitors to incorporate an aminobenzisoxazole as the P1 ligand resulted in compounds with improved selectivity for factor Xa relative to trypsin and plasma kallikrein. Further optimization of the P4 moiety led to compounds with enhanced permeability and reduced protein binding. The SAR and pharmacokinetic profile of this series of compounds is described herein. These efforts culminated in 1-(3′-aminobenzisoxazol-5′-yl)-3-trifluoromethyl-N-[2-fluoro-4- [(2′-dimethylaminomethyl)imidazol-1-yl]phenyl]-1H-pyrazole-5-carboxyamide (11d), a potent, selective, and orally bioavailable inhibitor of factor Xa. On the basis of its excellent in vitro potency and selectivity profile, high free fraction in human plasma, good oral bioavailability, and in vivo efficacy in antithrombotic models, the HCl salt of this compound was selected for clinical development as razaxaban (DPC 906, BMS-561389).
Substituted amino methyl factor Xa inhibitors
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, (2008/06/13)
The present application describes substituted-aminomethyl substituted compounds and derivatives thereof, or pharmaceutically acceptable salt forms thereof, which are useful as inhibitors of factor Xa.
