4YT6

Factor VIIa in complex with the inhibitor 4-{[(R)-[5-ethoxy-2-fluoro-3-(propan-2-yloxy)phenyl](4-phenyl-1H-imidazol-2-yl)methyl]amino}benzenecarboximidamide

Summary for 4YT6

• Entry DOI: 10.2210/pdb4yt6/pdb
• Related: 4YT7
• Descriptor: Coagulation factor VII (heavy chain), Coagulation factor VII (light chain), 4-[[(R)-(5-ethoxy-2-fluoranyl-3-propan-2-yloxy-phenyl)-(4-phenyl-1H-imidazol-2-yl)methyl]amino]benzenecarboximidamide, ... (7 entities in total)
• Functional Keywords: glycoprotein, hydrolase, serine protease, plasma, blood coagulation factor, protein inhibitor complex, calcium-binding, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Homo sapiens (Human); More
• Cellular location: Secreted: P08709 P08709
• Total number of polymer chains: 2
• Total formula weight: 35563.55

Authors

Wei, A. (deposition date: 2015-03-17, release date: 2015-04-29, Last modification date: 2024-10-09)

Primary citation

Glunz, P.W.,Cheng, X.,Cheney, D.L.,Weigelt, C.A.,Wei, A.,Luettgen, J.M.,Wong, P.C.,Wexler, R.R.,Priestley, E.S.
Design and synthesis of potent, selective phenylimidazole-based FVIIa inhibitors.
Bioorg.Med.Chem.Lett., 25:2169-2173, 2015

PubMed Abstract: Heterocyclic amide isosteres were incorporated into a phenylglycine-based tissue factor/factor VIIa (TF-FVIIa) inhibitor chemotype, providing potent inhibitors. An X-ray co-crystal structure of phenylimidazole 19 suggested that an imidazole nitrogen atom effectively mimics an amide carbonyl, while the phenyl ring forms key hydrophobic interactions with the S1' pocket. Exploration of phenylimidazole substitution led to the discovery of potent, selective and efficacious inhibitors of TF-FVIIa.

PubMed: 25881820
DOI: 10.1016/j.bmcl.2015.03.062

Experimental method

X-RAY DIFFRACTION (2.07 Å)