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Discovery of hydroxy pyrimidine Factor IXa inhibitors.

Charles L Jayne, Teresa Andreani, Tin-Yau Chan, Mariappan V Chelliah, Martin C Clasby, Michael Dwyer, Keith A Eagen, Steve Fried, William J Greenlee, Zhuyan Guo, Brian Hawes, Alan Hruza, Richard Ingram, Kartik M Keertikar, Santhosh Neelamkavil, Paul Reichert, Yan Xia, Samuel Chackalamannil
Bioorganic & Medicinal Chemistry Letters 2020 August 2
The synthesis and structure activity relationship development of a pyrimidine series of heterocyclic Factor IXa inhibitors is described. Increased selectivity over Factor Xa inhibition was achieved through SAR expansion of the P1 element. Select compounds were evaluated in vivo to assess their plasma levels in rat.

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