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PDBsum entry 2zeb
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References listed in PDB file
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Key reference
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Title
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Potent, Nonpeptide inhibitors of human mast cell tryptase. Synthesis and biological evaluation of novel spirocyclic piperidine amide derivatives.
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Authors
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M.J.Costanzo,
S.C.Yabut,
H.C.Zhang,
K.B.White,
L.De garavilla,
Y.Wang,
L.K.Minor,
B.A.Tounge,
A.N.Barnakov,
F.Lewandowski,
C.Milligan,
J.C.Spurlino,
W.M.Abraham,
V.Boswell-Smith,
C.P.Page,
B.E.Maryanoff.
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Ref.
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Bioorg Med Chem Lett, 2008,
18,
2114-2121.
[DOI no: ]
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PubMed id
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Abstract
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We have explored a series of spirocyclic piperidine amide derivatives (5) as
tryptase inhibitors. Thus, 4 (JNJ-27390467) was identified as a potent,
selective tryptase inhibitor with oral efficacy in two animal models of airway
inflammation (sheep and guinea pig asthma models). An X-ray co-crystal structure
of 4 x tryptase revealed a hydrophobic pocket in the enzyme's active site, which
is induced by the phenylethynyl group and is comprised of amino acid residues
from two different monomers of the tetrameric protein.
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