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PDBsum entry 5u6j
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Hydrolase/hydrolase inhibitor
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PDB id
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5u6j
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References listed in PDB file
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Key reference
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Title
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Neutral macrocyclic factor viia inhibitors.
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Authors
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N.R.Wurtz,
B.L.Parkhurst,
I.Delucca,
P.W.Glunz,
W.Jiang,
X.Zhang,
D.L.Cheney,
J.M.Bozarth,
A.R.Rendina,
A.Wei,
T.Harper,
J.M.Luettgen,
Y.Wu,
P.C.Wong,
D.A.Seiffert,
R.R.Wexler,
E.S.Priestley.
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Ref.
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Bioorg Med Chem Lett, 2017,
27,
2650-2654.
[DOI no: ]
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PubMed id
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Abstract
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Factor VIIa (FVIIa) inhibitors have shown strong antithrombotic efficacy in
preclinical thrombosis models with limited bleeding liabilities. Discovery of
potent, orally active FVIIa inhibitors has been largely unsuccessful due to the
requirement of a basic P1 group to interact with Asp189 in the S1 binding
pocket, limiting their membrane permeability. We have combined recently reported
neutral P1 binding substituents with a highly optimized macrocyclic chemotype to
produce FVIIa inhibitors with low nanomolar potency and enhanced permeability.
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