2. Academic Validation
  3. 1-(2-Naphthyl)-1H-pyrazole-5-carboxylamides as potent factor Xa inhibitors. Part 3: Design, synthesis and SAR of orally bioavailable benzamidine-P4 inhibitors

1-(2-Naphthyl)-1H-pyrazole-5-carboxylamides as potent factor Xa inhibitors. Part 3: Design, synthesis and SAR of orally bioavailable benzamidine-P4 inhibitors

  • Bioorg Med Chem Lett. 2004 Mar 8;14(5):1229-34. doi: 10.1016/j.bmcl.2003.12.054.
Zhaozhong J Jia 1,  Yanhong Wu,  Wenrong Huang,  Penglie Zhang,  Yonghong Song,  John Woolfrey,  Uma Sinha,  Ann E Arfsten,  Susan T Edwards,  Athiwat Hutchaleelaha,  Stanley J Hollennbach,  Joseph L Lambing,  Robert M Scarborough,  Bing-Yan Zhu
Affiliations

Affiliation

  • 1 Millennium Pharmaceuticals Inc., 256 East Grand Avenue, South San Francisco, CA 94080, USA. zjia@portola.com
PMID: 14980671 DOI: 10.1016/j.bmcl.2003.12.054
Abstract

Using N,N-dialkylated benzamidines as the novel P4 motifs, we have designed and synthesized a class of 1-(2-naphthyl)-1H-pyrazole-5-carboxylamides as highly potent and selective fXa inhibitors with significantly improved hydrophilicity and in vitro anticoagulant activity. These benzamidine-P4 fXa inhibitors have displayed excellent oral bioavailability and long half-life.

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