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PDBsum entry 4yzu
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Hydrolase/hydrolase inhibitor
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PDB id
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4yzu
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References listed in PDB file
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Key reference
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Title
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Rapid development of two factor ixa inhibitors from hit to lead.
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Authors
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D.L.Parker,
S.Walsh,
B.Li,
E.Kim,
A.Sharipour,
C.Smith,
Y.H.Chen,
R.Berger,
B.Harper,
T.Zhang,
M.Park,
M.Shu,
J.Wu,
J.Xu,
S.Dewnani,
E.C.Sherer,
A.Hruza,
P.Reichert,
W.Geissler,
L.Sonatore,
K.Ellsworth,
J.Balkovec,
W.Greenlee,
H.B.Wood.
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Ref.
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Bioorg Med Chem Lett, 2015,
25,
2321-2325.
[DOI no: ]
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PubMed id
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Abstract
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Two high-throughput screening hits were investigated for SAR against human
factor IXa. Both hits feature a benzamide linked to a [6-5]-heteroaryl via an
alkyl amine. In the case where this system is a benzimidazolyl-ethyl amine the
binding potency for the hit was improved >500-fold, from 9μM to 0.016μM.
For the other hit, which contains a tetrahydropyrido-indazole amine, potency was
improved 20-fold, from 2μM to 0.09μM. X-ray crystal structures were obtained
for an example of each class which improved understanding of the binding, and
will enable further drug discovery efforts.
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