1EAU

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

1EAU の概要

• エントリーDOI: 10.2210/pdb1eau/pdb
• 分子名称: PORCINE PANCREATIC ELASTASE, SODIUM ION, SULFATE ION, ... (5 entities in total)
• 機能のキーワード: hydrolase (serine protease)
• 由来する生物種: Sus scrofa (pig)
• 細胞内の位置: Secreted: P00772
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 26587.67

構造登録者

Ceccarelli, C. (登録日: 1994-11-22, 公開日: 1995-02-07, 最終更新日: 2024-10-30)

主引用文献

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

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: 7837235
DOI: 10.1021/jm00001a028

実験手法

X-RAY DIFFRACTION (2 Å)