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References listed in PDB file
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Key reference
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Title
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Nonpeptidic inhibitors of human leukocyte elastase. 5. Design, Synthesis, And X-Ray crystallography of a series of orally active 5-Aminopyrimidin-6-One-Containing trifluoromethyl ketones.
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Authors
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C.A.Veale,
P.R.Bernstein,
C.Bryant,
C.Ceccarelli,
J.R.Damewood,
R.Earley,
S.W.Feeney,
B.Gomes,
B.J.Kosmider,
G.B.Steelman.
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Ref.
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J Med Chem, 1995,
38,
98.
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PubMed id
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Abstract
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The effects of changes in substitution in a series of 5-amino-2-pyrimidin-6-ones
on both in vitro activity and oral activity in an acute hemorrhagic assay have
been explored. These compounds contained either a trifluoromethyl ketone or a
boronic acid moiety to bind covalently to the Ser-195 hydroxyl of human
leukocyte elastase (HLE). Boronic acid-containing inhibitors were found to be
more potent than the corresponding trifluoromethyl ketones in vitro but were
less active upon oral administration. Compound 13b was found to offer the best
combination of oral potency, duration of action, and enzyme selectivity and, as
such, was selected for further biological testing. X-ray crystallography of a
cocrystallized complex of compound 19m and porcine pancreatic elastase
demonstrated that the inhibitor is bound to the enzyme in a manner similar to
that found previously for a closely related series of pyridone-containing
inhibitors of HLE.
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Secondary reference #1
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Title
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Nonpeptidic inhibitors of human leukocyte elastase. 6. Design of a potent, Intratracheally active, Pyridone-Based trifluoromethyl ketone.
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Authors
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P.R.Bernstein,
B.C.Gomes,
B.J.Kosmider,
E.P.Vacek,
J.C.Williams.
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Ref.
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J Med Chem, 1995,
38,
212-215.
[DOI no: ]
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PubMed id
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Note: In the PDB file this reference is
annotated as "TO BE PUBLISHED". The citation details given above have
been manually determined.
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Secondary reference #2
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Title
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Nonpeptidic inhibitors of human leukocyte elastase. 4. Design, Synthesis,In vitro, And in vivo activity of a series of beta-Carbolinone-Containing trifluoromethyl ketones
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Authors
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C.A.Veale,
J.R.Damewood,
G.B.Steelman,
C.Bryant,
B.Gomes,
J.Williams.
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Ref.
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TO BE PUBLISHED ...
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Secondary reference #3
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Title
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Nonpeptidic inhibitors of human leukocyte elastase. 3. Design, Synthesis, X-Ray crystallographic analysis, And structure-Activity relationships for a series of orally active 3-Amino-6-Phenylpyridin-2-One trifluoromethyl ketones
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Authors
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P.R.Bernstein,
D.Andisik,
P.K.Bradley,
C.B.Bryant,
C.Ceccarelli,
J.R.Damewood,
R.Earley,
P.D.Edwards,
S.Feeney,
B.C.Gomes,
B.J.Kosmider,
G.B.Steelman,
R.M.Thomas,
E.P.Vacek,
C.A.Veale,
J.C.Williams,
D.J.Wolanin,
S.A.Woolson.
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Ref.
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j med chem, 1994,
37,
3313.
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Secondary reference #4
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Title
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Nonpeptidic inhibitors of human leukocyte elastase. 2. Design, Synthesis and in vitro activity of a series of 3-Amino-6-Arylpyridin-2-One trifluoromethyl ketones
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Authors
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J.R.Damewood,
P.D.Edwards,
S.Feeney,
B.C.Gomes,
G.B.Steelman,
P.A.Tuthill,
P.Warner,
J.C.Williams,
S.A.Woolson,
D.Wolanin,
C.Veale.
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Ref.
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j med chem, 1994,
37,
3303.
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Secondary reference #5
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Title
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Nonpeptidic inhibitors of human leukocyte elastase. 1. The design and synthesis of pyridone-Containing inhibitors
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Authors
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P.Warner,
R.C.Green,
B.C.Gomes,
J.C.Williams.
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Ref.
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j med chem, 1994,
37,
3090.
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Secondary reference #6
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Title
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Design of orally active, Nonpeptidic inhibitors of human leukocyte elastase
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Authors
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F.J.Brown,
D.W.Andisik,
P.R.Bernstein,
C.B.Bryant,
C.Ceccarelli,
J.R.Damewood,
P.D.Edwards,
R.Earley,
S.W.Feeney,
R.C.Green,
B.Gomes,
B.J.Kosmider,
R.Krell,
A.Shaw,
G.B.Steelman,
R.M.Thomas,
E.P.Vacek,
C.A.Veale,
P.A.Tuthill,
P.Warner,
J.C.Williams,
D.J.Wolanin,
S.A.Woolson.
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Ref.
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j med chem, 1994,
37,
1259.
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Secondary reference #7
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Title
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Design, Synthesis, And kinetic evaluation of a unique class of elastase inhibitors, The peptidyl alpha-Ketobenzoxazoles,And the x-Ray crystal structure of the covalent complex between porcine pancreatic elastase and ac-Ala-Pro-Val-2-Benzoxazole
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Authors
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P.D.Edwards,
E.F.Meyer,
J.Vijayalakshmi,
P.A.Tuthill,
D.A.Andisik,
B.Gomes,
A.Strimpler.
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Ref.
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j am chem soc, 1992,
114,
1854.
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Secondary reference #8
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Title
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Crystal structure of the covalent complex formed by a peptidyl alpha,Alpha-Difluoro-Beta-Keto amide with porcine pancreatic elastase at 1.78-Angstrom resolution
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Authors
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L.H.Takahashi,
R.Radhakrishnan,
R.E.Rosenfield,
E.F.Meyer,
D.A.Trainor.
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Ref.
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j am chem soc, 1989,
111,
3368.
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Secondary reference #9
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Title
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X-Ray diffraction analysis of the inhibition of porcine pancreatic elastase by a peptidyl trifluoromethylketone.
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Authors
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L.H.Takahashi,
R.Radhakrishnan,
R.E.Rosenfield,
E.F.Meyer,
D.A.Trainor,
M.Stein.
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Ref.
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J Mol Biol, 1988,
201,
423-428.
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PubMed id
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