1-(2-Naphthyl)-1H-pyrazole-5-carboxylamides as potent factor Xa inhibitors. Part 2: A survey of P4 motifs

…, ST Edwards, M Alphonso, A Hutchaleelaha…

Index: Jia, Zhaozhong J.; Wu, Yanhong; Huang, Wenrong; Zhang, Penglie; Clizbe, Lane A.; Goldman, Erick A.; Sinha, Uma; Arfsten, Ann E.; Edwards, Susan T.; Alphonso, Merlyn; Hutchaleelaha, Athiwat; Scarborough, Robert M.; Zhu, Bing-Yan Bioorganic and Medicinal Chemistry Letters, 2004 , vol. 14, # 5 p. 1221 - 1227

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Citation Number: 25

Abstract

A variety of P4 motifs have been examined to increase the binding affinity and in vitro anticoagulant potency of our biphenyl 1-(2-naphthyl)-1H-pyrazole-5-carboxylamide-based fXa inhibitors. Highly potent 2-naphthyl-P1 fXa inhibitors (Ki≤ 2 nM) with improved in vitro anticoagulant activity (2× TG≤ 1 μM) and respectable pharmacokinetic properties have been discovered.