Tripeptide aldehyde inhibitors of human rhinovirus 3C protease: Design, synthesis, biological evaluation, and cocrystal structure solution of P1 glutamine isosteric replacements

Journal of Medicinal Chemistry

Volumn 41, Issue 15, 1998, Pages 2786-2805

  Webber, Stephen E ^a   Okano, Koji ^a,b   Little, Thomas L ^a,c   Reich, Siegfried H ^a   Xin, Yue ^a,d   Fuhrman, Sheila A ^a   Matthews, David A ^a   Love, Robert A ^a   Hendrickson, Thomas F ^a   Patick, Amy K ^a   Meador III, James W ^a   Ferre, Rose Ann ^a   Brown, Edward L ^a   Ford, Clifford E ^a   Binford, Susan L ^a   Worland, Stephen T ^a  

^a AGOURON PHARMACEUTICALS INC   (United States)

^b Ctrl Pharmaceutical Res Institute   (Japan)

^c Molecumetics Ltd   (United States)

^d Chemical Abstracts Service   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIVIRUS AGENT; CYSTEINE PROTEINASE INHIBITOR;

ANTIVIRAL ACTIVITY; ARTICLE; CRYSTAL STRUCTURE; DRUG CONFORMATION; DRUG DESIGN; DRUG SYNTHESIS; HELA CELL; HUMAN; HUMAN CELL; HUMAN RHINOVIRUS; NONHUMAN; PROTEINASE INHIBITION; STRUCTURE ACTIVITY RELATION; VIRUS INHIBITION;

ANTIVIRAL AGENTS; BINDING SITES; CELL LINE, TRANSFORMED; CRYSTALLOGRAPHY, X-RAY; CYSTEINE ENDOPEPTIDASES; CYSTEINE PROTEINASE INHIBITORS; DRUG DESIGN; GLUTAMINE; HELA CELLS; HUMANS; MODELS, MOLECULAR; MOLECULAR CONFORMATION; OLIGOPEPTIDES; PROTEIN CONFORMATION; RHINOVIRUS; VIRAL PROTEINS;

EID: 14444269890     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm980071x     Document Type: Article

References (67)

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36. For example, see: (a) Aoyagi, T.; Umezawa, H. Structures and Activities of Protease Inhibitors of Microbial Origin. CoW Spring Harbor Conferences on Cell Proliferation; Cold Spring Harbor Laboratory: New York, 1975; Vol. 2; Protease and Biological Control, pp 429-454. (b) Westerik, J. O'C.; Wolfenden, R. Aldehydes as Inhibitors of Papain. J. Biol. Chem. 1972, 247, 8195-8197. (c) Thompson, R. C. Use of Peptide Aldehydes to Generate Transition-State Analogs of Elastase. Biochemistry 1973, 12, 47-51. (d) Bajusz, S.; Szell, E.; Badgy, D.; Barabas, E.; Horvath, G.; Dioszegi, M.; Fittler, Z.; Szabo, G.; Juhasz, A.; Tomori, E.; Szilagyi, G. Highly Active and Selective Anticoagulants: D-Phe-Pro-Arg-H, a Free Tripeptide Aldehyde Prone to Spontaneous Inactivation, and Its Stable N-Methyl Derivative, D-MePhe-Pro-Arg-H. J. Med. Chem. 1990, 33, 1729-1735. (e) Hassall, C. H.; Johnson, W. H.; Kennedy, A. J.; Roberts, N. A. A New Class of Inhibitors of Human Leucocyte Elastase. FEBS Lett. 1985, 183, 201-205. (f) Trainor, D. A. Synthetic Inhibitors of Human Neutrophil Elastase. Trends Pharmacol. Sci. 1987, 8, 303-307. (g) Chapman, K. T. Synthesis of a Potent, Reversible Inhibitor of Interleukin-1β Converting Enzyme. Bioorg. Med. Chem. Lett. 1992, 6, 613-618.
37. For example, see: (a) Aoyagi, T.; Umezawa, H. Structures and Activities of Protease Inhibitors of Microbial Origin. CoW Spring Harbor Conferences on Cell Proliferation; Cold Spring Harbor Laboratory: New York, 1975; Vol. 2; Protease and Biological Control, pp 429-454. (b) Westerik, J. O'C.; Wolfenden, R. Aldehydes as Inhibitors of Papain. J. Biol. Chem. 1972, 247, 8195-8197. (c) Thompson, R. C. Use of Peptide Aldehydes to Generate Transition-State Analogs of Elastase. Biochemistry 1973, 12, 47-51. (d) Bajusz, S.; Szell, E.; Badgy, D.; Barabas, E.; Horvath, G.; Dioszegi, M.; Fittler, Z.; Szabo, G.; Juhasz, A.; Tomori, E.; Szilagyi, G. Highly Active and Selective Anticoagulants: D-Phe-Pro-Arg-H, a Free Tripeptide Aldehyde Prone to Spontaneous Inactivation, and Its Stable N-Methyl Derivative, D-MePhe-Pro-Arg-H. J. Med. Chem. 1990, 33, 1729-1735. (e) Hassall, C. H.; Johnson, W. H.; Kennedy, A. J.; Roberts, N. A. A New Class of Inhibitors of Human Leucocyte Elastase. FEBS Lett. 1985, 183, 201-205. (f) Trainor, D. A. Synthetic Inhibitors of Human Neutrophil Elastase. Trends Pharmacol. Sci. 1987, 8, 303-307. (g) Chapman, K. T. Synthesis of a Potent, Reversible Inhibitor of Interleukin-1β Converting Enzyme. Bioorg. Med. Chem. Lett. 1992, 6, 613-618.
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