1eau: Difference between revisions

Revision as of 14:53, 2 May 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. 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 Fri May 2 14:53:05 2008

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

OCA

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 [[Image:1eau.jpg|left|200px]]
- {{Structure
+<!--
-|PDB= 1eau |SIZE=350|CAPTION= <scene name='initialview01'>1eau</scene>, resolution 2.0&Aring;
+The line below this paragraph, containing "STRUCTURE_1eau", creates the "Structure Box" on the page.
-|SITE=
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=BDK:2-[5-AMINO-6-OXO-2-(2-THIENYL)-1,6-DIHYDROPYRIMIDIN-1-YL)-N-[3,3-DIFLUORO+-1-ISOPROPYL-2-OXO-3-(N-(2-MORPHOLINO+ETHYL)CARBAMOYL]PROPYL]ACETAMIDE'>BDK</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|ACTIVITY= <span class='plainlinks'>[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] </span>
+or leave the SCENE parameter empty for the default display.
-|GENE=
+-->
-|DOMAIN=
+{{STRUCTURE_1eau|  PDB=1eau  |  SCENE=  }}
-|RELATEDENTRY=
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1eau FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1eau OCA], [http://www.ebi.ac.uk/pdbsum/1eau PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1eau RCSB]</span>
-}}
 '''NONPEPTIDIC INHIBITORS OF HUMAN LEUKOCYTE ELASTASE. 6. DESIGN OF A POTENT, INTRATRACHEALLY ACTIVE, PYRIDONE-BASED TRIFLUOROMETHYL KETONE'''
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 [[Category: Sus scrofa]]
 [[Category: Ceccarelli, C.]]
-[[Category: hydrolase (serine protease)]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May  2 14:53:05 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 19:58:54 2008''