Discovery and biological activity of orally active peptidyl trifluoromethyl ketone inhibitors of human neutrophil elastase

Journal of Medicinal Chemistry

Volumn 40, Issue 12, 1997, Pages 1876-1885

  Edwards, Philip D ^a   Andisik, Donald W ^a   Bryant, Craig A ^a   Ewing, Barbara ^a   Gomes, Bruce ^a   Lewis, Joseph J ^a   Rakiewicz, Donna ^a   Steelman, Gary ^a   Strimpler, Ann ^a   Trainor, Diane A ^a   Tuthill, Paul A ^a   Mauger, Russell C ^a   Veale, Chris A ^a   Wildonger, Richard A ^a   Williams, Joseph C ^a   Wolanin, Donald J ^a   Zottola, Mark ^a  

^a ASTRAZENECA   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

[(4 METHOXYPHENYL)CARBONYL]VALYL N [3 (1,1,1 TRIFLUORO 2 HYDROXY 4 METHYLPENTYL)]PROLINAMIDE; [4 (4 BROMOPHENYLSULFONYLCARBAMOYL)BENZOYL]VALYLPROLINE N (2 METHYL 1 TRIFLUOROACETYLPROPYL)AMIDE; ELASTASE INHIBITOR; N [4 [(4 CHLOROPHENYLSULFONYL)AMINOCARBONYL]BENZOYL]VALYLPROLYLVALYL TRIFLUOROMETHYL KETONE; TRIFLUOROMETHYL KETONE DERIVATIVE; UNCLASSIFIED DRUG;

AMINO TERMINAL SEQUENCE; ARTICLE; CHRONIC BRONCHITIS; CYSTIC FIBROSIS; DRUG ACTIVITY; LUNG DISEASE; LUNG EMPHYSEMA; LUNG WEIGHT;

ADMINISTRATION, ORAL; ANIMALS; BODY WEIGHT; CRICETINAE; DIPEPTIDES; ENZYME INHIBITORS; ERYTHROCYTE COUNT; HEMORRHAGE; HUMANS; LEUKOCYTE COUNT; LEUKOCYTE ELASTASE; LUNG; LUNG DISEASES; MALE; MESOCRICETUS; MOLECULAR STRUCTURE; ORGAN SIZE; STRUCTURE-ACTIVITY RELATIONSHIP; TRACHEA;

EID: 15144355533     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm960819g     Document Type: Article

References (32)

1. Abbreviations: AHA, acute hemorrhagic assay; ALIM, acute lung injury model; HNE, human neutrophil elastase; PPE, porcine pancreatic elastase; Ac, acetyl; Cbz, benzyloxycarbonyl; TFMK, trifluoromethyl ketone; PFEK, perfluoroethyl ketone; CAN, ceric ammonium nitrate; TEA, triethylamine; THF, tetrahydrofuran; DMSO, dimethyl sulfoxide; DMAP, (dimethylamino)pyridine; DCC, dicyclohexylcarbodiimide; MCPBA, m-chloroperbenzoic acid; EDAC, 1-ethyl-3-[3-(dimethylamino)propyl]-carbodiimide hydrochloride; HOBt, 1-hydroxybenzotriazole monohydrate; TBAF, tetra-n-butylammonium fluoride; TFA, trifluoroacetic acid; DMF, dimethylformamide; NMM, N-methylmorpholine; DMP, Dess-Martin periodinane, 1,1,1-triacetoxy-1,1-dihydro-1,2-benziodoxol-3(1H)-one; MeO, methoxy; Suc, succinyl; pNa, p-nitroanilide; PEG, polyethylene glycol; PBS, phosphate-buffered saline; ip, intraperitoneal; po, oral; it, intratracheal.
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