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PDBsum entry 2pr3
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Blood clotting
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PDB id
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2pr3
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References listed in PDB file
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Key reference
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Title
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Structure-Based drug design of pyrrolidine-1, 2-Dicarboxamides as a novel series of orally bioavailable factor xa inhibitors.
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Authors
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C.A.Van huis,
C.F.Bigge,
A.Casimiro-Garcia,
W.L.Cody,
D.A.Dudley,
K.J.Filipski,
R.J.Heemstra,
J.T.Kohrt,
L.S.Narasimhan,
R.P.Schaum,
E.Zhang,
J.W.Bryant,
S.Haarer,
N.Janiczek,
R.J.Leadley,
T.Mcclanahan,
J.Thomas peterson,
K.M.Welch,
J.J.Edmunds.
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Ref.
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Chem Biol Drug Des, 2007,
69,
444-450.
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PubMed id
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Abstract
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A novel series of pyrrolidine-1,2-dicarboxamides was discovered as factor Xa
inhibitors using structure-based drug design. This series consisted of a neutral
4-chlorophenylurea P1, a biphenylsulfonamide P4 and a D-proline scaffold (1,
IC(50) = 18 nM). Optimization of the initial hit resulted in an orally
bioavailable, subnanomolar inhibitor of factor Xa (13, IC(50) = 0.38 nM), which
was shown to be efficacious in a canine electrolytic model of thrombosis with
minimal bleeding.
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