PDBsum entry 4yt7

Hydrolase/hydrolase inhibitor

PDB id: 4yt7

Contents

Protein chains

254 a.a.

57 a.a.

Ligands

4K1

SO4 ×4

GOL ×2

Metals

_CA

Waters ×248

References listed in PDB file

Key reference

• Title: Design and synthesis of potent, Selective phenylimidazole-Based fviia inhibitors.
• Authors: P.W.Glunz, X.Cheng, D.L.Cheney, C.A.Weigelt, A.Wei, J.M.Luettgen, P.C.Wong, R.R.Wexler, E.S.Priestley.
• Ref.: Bioorg Med Chem Lett, 2015, 25, 2169-2173. [DOI no: 10.1016/j.bmcl.2015.03.062]
• PubMed id: 25881820

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.