Sulfonamidopyrrolidinone factor Xa inhibitors: potency and selectivity enhancements via P-1 and P-4 optimization

YM Choi-Sledeski, DG McGarry…

Index: Choi-Sledeski, Yong Mi; McGarry, Daniel G.; Green, Daniel M.; Mason, Helen J.; Becker, Michael R.; Davis, Roderick S.; Ewing, William R.; Dankulich, William P.; Manetta, Vincent E.; Morris, Robert L.; Spada, Alfred P.; Cheney, Daniel L.; Brown, Karen D.; Colussi, Dennis J.; Valeria, Chu; Heran, Christopher L.; Morgan, Suzanne R.; Bentley, Ross G.; Leadley, Robert J.; Maignan, Sebastien; Guilloteau, Jean-Pierre; Dunwiddie, Christopher T.; Pauls, Henry W. Journal of Medicinal Chemistry, 1999 , vol. 42, # 18 p. 3572 - 3587

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Citation Number: 44

Abstract

Sulfonamidopyrrolidinones were previously disclosed as a selective class of factor Xa (fXa) inhibitors, culminating in the identification of RPR120844 as a potent member with efficacy in vivo. Recognizing the usefulness of the central pyrrolidinone template for the presentation of ligands to the S-1 and S-4 subsites of fXa, studies to optimize the P-1 and P-4 groups were initiated. Sulfonamidopyrrolidinones containing 4-hydroxy-and 4- ...