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PDBsum entry 2c4f
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Contents |
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254 a.a.
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139 a.a.
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75 a.a.
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116 a.a.
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References listed in PDB file
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Key reference
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Title
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The discovery of fluoropyridine-Based inhibitors of the factor viia/tf complex--Part 2.
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Authors
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J.T.Kohrt,
K.J.Filipski,
W.L.Cody,
C.Cai,
D.A.Dudley,
C.A.Van huis,
J.A.Willardsen,
L.S.Narasimhan,
E.Zhang,
S.T.Rapundalo,
K.Saiya-Cork,
R.J.Leadley,
J.J.Edmunds.
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Ref.
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Bioorg Med Chem Lett, 2006,
16,
1060-1064.
[DOI no: ]
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PubMed id
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Abstract
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The activated factor VII/tissue factor complex (FVIIa/TF) is known to play a key
role in the formation of blood clots. Inhibition of this complex may lead to new
antithrombotic drugs. A fluoropyridine-based series of FVIIa/TF inhibitors was
discovered which utilized a diisopropylamino group for binding in the S2 and S3
binding pockets of the active site of the enzyme complex. In this series, an
enhancement in binding affinity was observed by substitution at the 5-position
of the hydroxybenzoic acid sidechain. An X-ray crystal structure indicates that
amides at this position may increase inhibitor binding affinity through
interactions with the S1'/S2' pocket.
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