2PHB

An Orally Efficacious Factor Xa Inhibitor

Summary for 2PHB

• Entry DOI: 10.2210/pdb2phb/pdb
• Descriptor: Coagulation factor X, heavy chain, Coagulation factor X, light chain, CALCIUM ION, ... (5 entities in total)
• Functional Keywords: fxa coagulation factor inhibitor, blood clotting
• Biological source: Homo sapiens (human); More
• Cellular location: Secreted: P00742 P00742
• Total number of polymer chains: 2
• Total formula weight: 32432.14

Authors

Zhang, E.,Kohrt, J.T.,Bigge, C.F.,Finzel, B.C. (deposition date: 2007-04-10, release date: 2008-03-25, Last modification date: 2017-10-18)

Primary citation

Kohrt, J.T.,Bigge, C.F.,Bryant, J.W.,Casimiro-Garcia, A.,Chi, L.,Cody, W.L.,Dahring, T.,Dudley, D.A.,Filipski, K.J.,Haarer, S.,Heemstra, R.,Janiczek, N.,Narasimhan, L.,McClanahan, T.,Peterson, J.T.,Sahasrabudhe, V.,Schaum, R.,Van Huis, C.A.,Welch, K.M.,Zhang, E.,Leadley, R.J.,Edmunds, J.J.
The discovery of (2R,4R)-N-(4-chlorophenyl)-N- (2-fluoro-4-(2-oxopyridin-1(2H)-yl)phenyl)-4-methoxypyrrolidine-1,2-dicarboxamide (PD 0348292), an orally efficacious factor Xa inhibitor
Chem.Biol.Drug Des., 70:100-112, 2007

PubMed Abstract: Herein, we report the discovery of novel, proline-based factor Xa inhibitors containing a neutral P1 chlorophenyl pharmacophore. Through the additional incorporation of 1-(4-amino-3-fluoro-phenyl)-1H-pyridin-2-one 22, as a P4 pharmacophore, we discovered compound 7 (PD 0348292). This compound is a selective, orally bioavailable, efficacious FXa inhibitor that is currently in phase II clinical trials for the treatment and prevention of thrombotic disorders.

PubMed: 17683371
DOI: 10.1111/j.1747-0285.2007.00539.x

Experimental method

X-RAY DIFFRACTION (2.3 Å)