6X5J

Discovery of Hydroxy Pyrimidine Factor IXa Inhibitors

Summary for 6X5J

• Entry DOI: 10.2210/pdb6x5j/pdb
• Related: 6X5L 6X5P
• Descriptor: Coagulation factor IX, GLYCEROL, 2-(4-HYDROXY-5-PHENYL-1H-PYRAZOL-3-YL)-1H-BENZOIMIDAZOLE-5-CARBOXAMIDINE, ... (7 entities in total)
• Functional Keywords: serine protease, zymogen, hydrolase, glycoprotein, hydroxylation, phosphoprotein, sulfation, hemostasis, hemophilia, xase-like variant, communication channel, gamma-carboxyglutamic acid, egf-like domain, disease mutation, blood clotting
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 34326.63

Authors

Jayne, C.L.,Andreani, T.,Chan, T.,Chelliah, M.V.,Clasby, M.C.,Dwyer, M.,Eagen, K.A.,Fried, S.,Greenlee, W.J.,Guo, Z.,Hawes, B.,Hruza, A.,Ingram, R.,Keertikar, K.M.,Neelamkavil, S.,Reichert, P.,Xia, Y.,Chackalamannil, S. (deposition date: 2020-05-26, release date: 2020-06-24)

Primary citation

Jayne, C.L.,Andreani, T.,Chan, T.Y.,Chelliah, M.V.,Clasby, M.C.,Dwyer, M.,Eagen, K.A.,Fried, S.,Greenlee, W.J.,Guo, Z.,Hawes, B.,Hruza, A.,Ingram, R.,Keertikar, K.M.,Neelamkavil, S.,Reichert, P.,Xia, Y.,Chackalamannil, S.
Discovery of hydroxy pyrimidine Factor IXa inhibitors.
Bioorg.Med.Chem.Lett., 30:127279-127279, 2020

PubMed Abstract: 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.

PubMed: 32527459
DOI: 10.1016/j.bmcl.2020.127279

Experimental method

X-RAY DIFFRACTION (2.513 Å)