1EAU
NONPEPTIDIC INHIBITORS OF HUMAN LEUKOCYTE ELASTASE. 6. DESIGN OF A POTENT, INTRATRACHEALLY ACTIVE, PYRIDONE-BASED TRIFLUOROMETHYL KETONE
Summary for 1EAU
| Entry DOI | 10.2210/pdb1eau/pdb |
| Descriptor | PORCINE PANCREATIC ELASTASE, SODIUM ION, SULFATE ION, ... (5 entities in total) |
| Functional Keywords | hydrolase (serine protease) |
| Biological source | Sus scrofa (pig) |
| Cellular location | Secreted: P00772 |
| Total number of polymer chains | 1 |
| Total formula weight | 26587.67 |
| Authors | Ceccarelli, C. (deposition date: 1994-11-22, release date: 1995-02-07, Last modification date: 2024-10-30) |
| Primary citation | Bernstein, P.R.,Gomes, B.C.,Kosmider, B.J.,Vacek, E.P.,Williams, J.C. Nonpeptidic inhibitors of human leukocyte elastase. 6. Design of a potent, intratracheally active, pyridone-based trifluoromethyl ketone. J.Med.Chem., 38:212-215, 1995 Cited by PubMed Abstract: 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. PubMed: 7837235DOI: 10.1021/jm00001a028 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2 Å) |
Structure validation
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