1eat
From Proteopedia
| Line 1: | Line 1: | ||
[[Image:1eat.gif|left|200px]] | [[Image:1eat.gif|left|200px]] | ||
| - | + | <!-- | |
| - | + | The line below this paragraph, containing "STRUCTURE_1eat", creates the "Structure Box" on the page. | |
| - | + | You may change the PDB parameter (which sets the PDB file loaded into the applet) | |
| - | + | or the SCENE parameter (which sets the initial scene displayed when the page is loaded), | |
| - | + | or leave the SCENE parameter empty for the default display. | |
| - | | | + | --> |
| - | | | + | {{STRUCTURE_1eat| PDB=1eat | SCENE= }} |
| - | + | ||
| - | + | ||
| - | }} | + | |
'''NONPEPTIDIC INHIBITORS OF HUMAN LEUKOCYTE ELASTASE. 5. DESIGN, SYNTHESIS, AND X-RAY CRYSTALLOGRAPHY OF A SERIES OF ORALLY ACTIVE 5-AMINO-PYRIMIDIN-6-ONE-CONTAINING TRIFLUOROMETHYLKETONES''' | '''NONPEPTIDIC INHIBITORS OF HUMAN LEUKOCYTE ELASTASE. 5. DESIGN, SYNTHESIS, AND X-RAY CRYSTALLOGRAPHY OF A SERIES OF ORALLY ACTIVE 5-AMINO-PYRIMIDIN-6-ONE-CONTAINING TRIFLUOROMETHYLKETONES''' | ||
| Line 27: | Line 24: | ||
[[Category: Sus scrofa]] | [[Category: Sus scrofa]] | ||
[[Category: Ceccarelli, C.]] | [[Category: Ceccarelli, C.]] | ||
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 14:52:56 2008'' | |
| - | + | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 11:52, 2 May 2008
NONPEPTIDIC INHIBITORS OF HUMAN LEUKOCYTE ELASTASE. 5. DESIGN, SYNTHESIS, AND X-RAY CRYSTALLOGRAPHY OF A SERIES OF ORALLY ACTIVE 5-AMINO-PYRIMIDIN-6-ONE-CONTAINING TRIFLUOROMETHYLKETONES
Overview
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.
About this Structure
1EAT is a Single protein structure of sequence from Sus scrofa. Full crystallographic information is available from OCA.
Reference
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., Veale CA, Bernstein PR, Bryant C, Ceccarelli C, Damewood JR Jr, Earley R, Feeney SW, Gomes B, Kosmider BJ, Steelman GB, et al., J Med Chem. 1995 Jan 6;38(1):98-108. PMID:7837246 Page seeded by OCA on Fri May 2 14:52:56 2008
