1eau: Difference between revisions

Revision as of 13:25, 21 February 2008

NONPEPTIDIC INHIBITORS OF HUMAN LEUKOCYTE ELASTASE. 6. DESIGN OF A POTENT, INTRATRACHEALLY ACTIVE, PYRIDONE-BASED TRIFLUOROMETHYL KETONE

OverviewOverview

Further modification of the 3-amino substituent in a trifluoromethyl ketone-based series of 3-amino-6-phenylpyridin-2-ones that had been optimized for oral activity led to analogs that were potent intratracheal inhibitors in a model of HLE-induced lung damage in the hamster. The best 3-amino substituent for intratracheal activity is [4-[N-[(4-chlorophenyl)sulfonyl]-carbamoyl]phenyl]sulfonyl. At a 30 min prechallenge interval, compound 9, which incorporates this substituent, had an ED50 of approximately 2 nmol/animal and, qualitatively, afforded a very similar dose-response relationship to that found with a peptidic trifluoromethyl ketone inhibitor, ICI 200,355.

About this StructureAbout this Structure

1EAU is a Single protein structure of sequence from Sus scrofa with , and as ligands. Active as Pancreatic elastase, with EC number 3.4.21.36 Full crystallographic information is available from OCA.

ReferenceReference

Nonpeptidic inhibitors of human leukocyte elastase. 6. Design of a potent, intratracheally active, pyridone-based trifluoromethyl ketone., Bernstein PR, Gomes BC, Kosmider BJ, Vacek EP, Williams JC, J Med Chem. 1995 Jan 6;38(1):212-5. PMID:7837235

Page seeded by OCA on Thu Feb 21 12:25:48 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
-[[Image:1eau.jpg|left|200px]]<br /><applet load="1eau" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1eau.jpg|left|200px]]<br /><applet load="1eau" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1eau, resolution 2.0&Aring;" />
 '''NONPEPTIDIC INHIBITORS OF HUMAN LEUKOCYTE ELASTASE. 6. DESIGN OF A POTENT, INTRATRACHEALLY ACTIVE, PYRIDONE-BASED TRIFLUOROMETHYL KETONE'''<br />
 ==Overview==
-Further modification of the 3-amino substituent in a trifluoromethyl, ketone-based series of 3-amino-6-phenylpyridin-2-ones that had been, optimized for oral activity led to analogs that were potent intratracheal, inhibitors in a model of HLE-induced lung damage in the hamster. The best, 3-amino substituent for intratracheal activity is, [4-[N-[(4-chlorophenyl)sulfonyl]-carbamoyl]phenyl]sulfonyl. At a 30 min, prechallenge interval, compound 9, which incorporates this substituent, had an ED50 of approximately 2 nmol/animal and, qualitatively, afforded a, very similar dose-response relationship to that found with a peptidic, trifluoromethyl ketone inhibitor, ICI 200,355.
+Further modification of the 3-amino substituent in a trifluoromethyl ketone-based series of 3-amino-6-phenylpyridin-2-ones that had been optimized for oral activity led to analogs that were potent intratracheal inhibitors in a model of HLE-induced lung damage in the hamster. The best 3-amino substituent for intratracheal activity is [4-[N-[(4-chlorophenyl)sulfonyl]-carbamoyl]phenyl]sulfonyl. At a 30 min prechallenge interval, compound 9, which incorporates this substituent, had an ED50 of approximately 2 nmol/animal and, qualitatively, afforded a very similar dose-response relationship to that found with a peptidic trifluoromethyl ketone inhibitor, ICI 200,355.
 ==About this Structure==
-EAU is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa] with NA, SO4 and BDK as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Pancreatic_elastase Pancreatic elastase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.36 3.4.21.36] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1EAU OCA].
+EAU is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa] with <scene name='pdbligand=NA:'>NA</scene>, <scene name='pdbligand=SO4:'>SO4</scene> and <scene name='pdbligand=BDK:'>BDK</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Pancreatic_elastase Pancreatic elastase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.36 3.4.21.36] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1EAU OCA].
 ==Reference==
@@ Line 20: / Line 20: @@
 [[Category: hydrolase (serine protease)]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 13:52:04 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:25:48 2008''