Potent, small-molecule inhibitors of human mast cell tryptase. Antiasthmatic action of a dipeptide-based transition-state analogue containing a benzothiazole ketone

Journal of Medicinal Chemistry

Volumn 46, Issue 18, 2003, Pages 3865-3876

  Costanzo, Michael J ^a   Yabut, Stephen C ^a   Almond Jr , Harold R ^a   Andrade Gordon, Patricia ^a   Corcoran, Thomas W ^a   De Garavilla, Lawrence ^a   Kauffman, Jack A ^a   Abraham, William M ^b   Recacha, Rosario ^c   Chattopadhyay, Debashish ^c   Maryanoff, Bruce E ^a  

^a JOHNSON AND JOHNSON PHARMACEUTICAL RESEARCH AND DEVELOPMENT   (United States)

^b UNIVERSITY OF MIAMI   (United States)

^c UNIVERSITY OF ALABAMA AT BIRMINGHAM   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1 ACETYL N [4 [(AMINOIMINOMETHYL)AMINO] 1 (2 BENZOTHIAZOLYLCARBONYL)BUTYL] 2 PYRROLIDINECARBOXAMIDE; 1 ACETYL N [4 [(AMINOIMINOMETHYL)AMINO] 1 (2 BENZOTHIAZOLYLCARBONYL)BUTYL] 2,5 DIHYDRO 1H PYRROLE 2 CARBOXAMIDE; 1 ACETYL N [4 [(AMINOIMINOMETHYL)AMINO] 1 (2 BENZOTHIAZOLYLCARBONYL)BUTYL] 4 HYDROXY 2 PYRROLIDINECARBOXAMIDE; 1 ACETYL N [4 [(AMINOIMINOMETHYL)AMINO] 1 (2 NEMZOTHIAZOLYLCARBONYL)BUTYL] 2 AZETIDINECARBOXAMIDE; 2 (ACETYLAMINO) N [4 [(AMINOIMINOMETHYL)AMINO] 1 (2 BENZOTHIAZOLYLCARBONYL)BUTYL] 4 METHYLPENTANAMIDE; ANTIASTHMATIC AGENT; ANTIGEN; BENZOTHIAZOLE DERIVATIVE; CARBACHOL; CYCLOPENTANE DERIVATIVE; DIPEPTIDE; GLUTAMINE; HISTIDINE; KALLIKREIN; KETONE; N (1 HYDROXY 2 NAPHTHOYL)ARGINYLPROLINAMIDE; N [4 [(AMINOIMINOMETHYL)AMINO] 1 (2 BENZOTHIAZOLYLCARBONYL)BUTYL]CYCLOPENTANECARBOXAMIDE; PLASMIN; RWJ 56423; RWJ 58643; SERINE; SERINE PROTEINASE; SODIUM SULFATE; THROMBIN; TRYPSIN; TRYPTASE; TRYPTASE INHIBITOR; UNCLASSIFIED DRUG;

AEROSOL; ALLERGIC ASTHMA; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BRONCHUS HYPERREACTIVITY; CATTLE; CONTROLLED STUDY; CRYSTAL STRUCTURE; DRUG ACTIVITY; DRUG ANTAGONISM; DRUG POTENCY; DRUG SELECTIVITY; ENZYME ACTIVITY; ENZYME ASSAY; ENZYME INHIBITION; HUMAN; HUMAN CELL; HYDROGEN BOND; IMMUNE RESPONSE; MAST CELL; MOLECULAR WEIGHT; MOLECULE; NONHUMAN; SHEEP; STEREOCHEMISTRY; X RAY CRYSTALLOGRAPHY;

AEROSOLS; ANIMALS; ANTI-ASTHMATIC AGENTS; ASTHMA; BENZOTHIAZOLES; CATTLE; CRYSTALLOGRAPHY, X-RAY; DIPEPTIDES; HUMANS; KETONES; KINETICS; MAST CELLS; MODELS, MOLECULAR; PROTEIN BINDING; PYRROLIDINES; SERINE ENDOPEPTIDASES; SERINE PROTEINASE INHIBITORS; SHEEP; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP; THIAZOLES; TRYPSIN; TRYPTASES;

EID: 0042921559     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm030050p     Document Type: Article

References (51)

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49. For information relative to the increased electron-withdrawing nature of benzothiazole relative to thiazole, see: (a) Chan, A. W. E.; Golec, J. M. C. Prediction of relative potency of ketone protease inhibitors using molecular orbital theory. Bioorg. Med. Chem. 1996, 4, 1673-1677. (b) Edwards, P. D.; Wolanin, D. J.; Andisik, D. W.; Davis, M. W. Peptidyl α-ketoheterocyclic inhibitors of human neutrophil elastase. 2. Effect of varying the heterocyclic ring on in vitro potency. J. Med. Chem. 1995, 38, 76-85. (c) Reference 8a.
50. For information relative to the increased electron-withdrawing nature of benzothiazole relative to thiazole, see: (a) Chan, A. W. E.; Golec, J. M. C. Prediction of relative potency of ketone protease inhibitors using molecular orbital theory. Bioorg. Med. Chem. 1996, 4, 1673-1677. (b) Edwards, P. D.; Wolanin, D. J.; Andisik, D. W.; Davis, M. W. Peptidyl α-ketoheterocyclic inhibitors of human neutrophil elastase. 2. Effect of varying the heterocyclic ring on in vitro potency. J. Med. Chem. 1995, 38, 76-85. (c) Reference 8a.
51. See the paragraph at the end of this paper regarding Supporting Information.