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
  • 1. Millennium Pharmaceuticals Inc., 256 East Grand Avenue, South San Francisco, CA 94080, USA. [email protected]
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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