Discovery of betrixaban (PRT054021), N-(5-chloropyridin-2-yl)-2-(4-(N,N-dimethylcarbamimidoyl)benzamido)-5-methoxybenzamide, a highly potent, selective, and orally efficacious factor Xa inhibitor

  • Bioorg Med Chem Lett. 2009 Apr 15;19(8):2179-85. doi: 10.1016/j.bmcl.2009.02.111.
Penglie Zhang  1 ,  Wenrong Huang ,  Lingyan Wang ,  Liang Bao ,  Zhaozhong J Jia ,  Shawn M Bauer ,  Erick A Goldman ,  Gary D Probst ,  Yonghong Song ,  Ting Su ,  Jingmei Fan ,  Yanhong Wu ,  Wenhao Li ,  John Woolfrey ,  Uma Sinha ,  Paul W Wong ,  Susan T Edwards ,  Ann E Arfsten ,  Lane A Clizbe ,  James Kanter ,  Anjali Pandey ,  Gary Park ,  Athiwat Hutchaleelaha ,  Joseph L Lambing ,  Stanley J Hollenbach ,  Robert M Scarborough ,  Bing-Yan Zhu
Affiliations
  • 1. Millennium Pharmaceuticals, Inc, South San Francisco, CA 94080, USA.
PMID: 19297154 DOI: 10.1016/j.bmcl.2009.02.111
Abstract

Systematic SAR studies of in vitro Factor Xa inhibitory activity around compound 1 were performed by modifying each of the three phenyl rings. A class of highly potent, selective, efficacious and orally bioavailable direct Factor Xa inhibitors was discovered. These compounds were screened in hERG binding assays to examine the effects of substitution groups on the hERG channel affinity. From the leading compounds, betrixaban (compound 11, PRT054021) has been selected as the clinical candidate for development.

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