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Title
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Macrocyclic factor XIa inhibitors.
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Authors
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C.Wang,
J.R.Corte,
K.A.Rossi,
J.M.Bozarth,
Y.Wu,
S.Sheriff,
J.E.Myers,
J.M.Luettgen,
D.A.Seiffert,
R.R.Wexler,
M.L.Quan.
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Ref.
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Bioorg Med Chem Lett, 2017,
27,
4056-4060.
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PubMed id
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Abstract
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A series of macrocyclic factor XIa (FXIa) inhibitors was designed based on an
analysis of the crystal structures of the acyclic phenylimidazole compounds.
Further optimization using structure-based design led to inhibitors with pM
affinity for FXIa, excellent selectivity against a panel of relevant serine
proteases, and good potency in the activated partial thromboplastin time (aPTT)
clotting assay.
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