Discovery of 1-(3'-Aminobenzisoxazol-5'-yl)-3-trifluoromethyl-N-[2-fluoro-4-[(2'-dimethylaminomethyl) imidazol-1-yl] phenyl]-1 H-pyrazole-5-carboxyamide …

…, CA Teleha, JH Sun, RS Alexander, S Bai…

文献索引：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. Journal of Medicinal Chemistry, 2005 , vol. 48, # 6 p. 1729 - 1744

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被引用次数: 161

摘要

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 ...