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PDBsum entry 3sw2
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Hydrolase/hydrolase inhibitor
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PDB id
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3sw2
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References listed in PDB file
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Key reference
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Title
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Arylsulfonamidopiperidone derivatives as a novel class of factor xa inhibitors.
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Authors
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Y.Shi,
S.P.O'Connor,
D.Sitkoff,
J.Zhang,
M.Shi,
S.N.Bisaha,
Y.Wang,
C.Li,
Z.Ruan,
R.M.Lawrence,
H.E.Klei,
K.Kish,
E.C.Liu,
S.M.Seiler,
L.Schweizer,
T.E.Steinbacher,
W.A.Schumacher,
J.A.Robl,
J.E.Macor,
K.S.Atwal,
P.D.Stein.
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Ref.
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Bioorg Med Chem Lett, 2011,
21,
7516-7521.
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PubMed id
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Abstract
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The design, synthesis and SAR of a novel class of valerolactam-based
arylsulfonamides as potent and selective FXa inhibitors is reported. The
arylsulfonamide-valerolactam scaffold was derived based on the proposed
bioisosterism to the arylcyanoguanidine-caprolactam core in known FXa
inhibitors. The SAR study led to compound 46 as the most potent FXa inhibitor in
this series, with an IC(50) of 7 nM and EC(2×PT) of 1.7 μM. The X-ray
structure of compound 40 bound to FXa shows that the sulfonamide-valerolactam
scaffold anchors the aryl group in the S1 and the novel acylcytisine
pharmacophore in the S4 pockets.
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