Structure-based design of ketone-containing, tripeptidyl human rhinovirus 3C protease inhibitors

被引:40
作者
Dragovich, PS
Zhou, R
Webber, SE
Prins, TJ
Kwok, AK
Okano, K
Fuhrman, SA
Zalman, LS
Maldonado, FC
Brown, EL
Meador, JW
Patick, AK
Ford, CE
Brothers, MA
Binford, SL
Matthews, DA
Ferre, RA
Worland, ST
机构
[1] Agouron Pharmaceut Inc, San Diego, CA 92121 USA
[2] Japan Tobacco Inc, Cent Pharmaceut Res Inst, Osaka 56911, Japan
关键词
D O I
10.1016/S0960-894X(99)00587-9
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Tripeptide-derived molecules incorporating C-terminal ketone electrophiles were evaluated as reversible inhibitors of the cysteine-containing human rhinovirus 3C protease (3CP). An optimized example of such compounds displayed potent 3CP inhibition activity (K-i = 0.0045 mu M) and in vitro antiviral properties (EC50 = 0.34 mu M) when tested against HRV serotype-14. (C) 1999 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:45 / 48
页数:4
相关论文
共 26 条
  • [1] Peptidyl alpha-keto thiazole as potent thrombin inhibitors
    Akiyama, Y
    Tsutsumi, S
    Hatsushiba, E
    Ohuchi, S
    Okonogi, T
    [J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1997, 7 (05) : 533 - 538
  • [2] CORDINGLEY MG, 1990, J BIOL CHEM, V265, P9062
  • [3] Potent thrombin inhibitors that probe the S-1' subsite: Tripeptide transition state analogues based on a heterocycle-activated carbonyl group
    Costanzo, MJ
    Maryanoff, BE
    Hecker, LR
    Schott, MR
    Yabut, SC
    Zhang, HC
    AndradeGordon, P
    Kauffman, JA
    Lewis, JM
    Krishnan, R
    Tulinsky, A
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 1996, 39 (16) : 3039 - 3043
  • [4] COUCH RB, 1996, FIELDS VIROLOGY, V1, P713
  • [5] Structure-based design of irreversible, tripeptidyl human rhinovirus 3C protease inhibitors containing N-methyl amino acids
    Dragovich, PS
    Webber, SE
    Prins, TJ
    Zhou, R
    Marakovits, JT
    Tikhe, JG
    Fuhrman, SA
    Patick, AK
    Matthews, DA
    Ford, CE
    Brown, EL
    Binford, SL
    Meador, JW
    Ferre, RA
    Worland, ST
    [J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1999, 9 (15) : 2189 - 2194
  • [6] Structure-based design, synthesis, and biological evaluation of irreversible human rhinovirus 3C protease inhibitors. 1. Michael acceptor structure-activity studies
    Dragovich, PS
    Webber, SE
    Babine, RE
    Fuhrman, SA
    Patick, AK
    Matthews, DA
    Lee, CA
    Reich, SH
    Prins, TJ
    Marakovits, JT
    Littlefield, ES
    Zhou, R
    Tikhe, J
    Ford, CE
    Wallace, MB
    Meador, JW
    Ferre, RA
    Brown, EL
    Binford, SL
    Harr, JEV
    DeLisle, DM
    Worland, ST
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 1998, 41 (15) : 2806 - 2818
  • [7] Structure-based design, synthesis, and biological evaluation of irreversible human rhinovirus 3C protease inhibitors.: 4.: Incorporation of P1 lactam moieties as L-glutamine replacements
    Dragovich, PS
    Prins, TJ
    Zhou, R
    Webber, SE
    Marakovits, JT
    Fuhrman, SA
    Patick, AK
    Matthews, DA
    Lee, CA
    Ford, CE
    Burke, BJ
    Rejto, PA
    Hendrickson, TF
    Tuntland, T
    Brown, EL
    Meador, JW
    Ferre, RA
    Harr, JEV
    Kosa, MB
    Worland, ST
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 1999, 42 (07) : 1213 - 1224
  • [8] PEPTIDYL ALPHA-KETOHETEROCYCLIC INHIBITORS OF HUMAN NEUTROPHIL ELASTASE .3. IN-VITRO AND IN-VIVO POTENCY OF A SERIES OF PEPTIDYL ALPHA-KETOBENZOXAZOLES
    EDWARDS, PD
    ZOTTOLA, MA
    DAVIS, M
    WILLIAMS, J
    TUTHILL, PA
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 1995, 38 (20) : 3972 - 3982
  • [9] PEPTIDYL ALPHA-KETOHETEROCYCLIC INHIBITORS OF HUMAN NEUTROPHIL ELASTASE .2. EFFECT OF VARYING THE HETEROCYCLIC RING ON IN-VITRO POTENCY
    EDWARDS, PD
    WOLANIN, DJ
    ANDISIK, DW
    DAVIS, MW
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 1995, 38 (01) : 76 - 85
  • [10] DESIGN, SYNTHESIS, AND KINETIC EVALUATION OF A UNIQUE CLASS OF ELASTASE INHIBITORS, THE PEPTIDYL ALPHA-KETOBENZOXAZOLES, AND THE X-RAY CRYSTAL-STRUCTURE OF THE COVALENT COMPLEX BETWEEN PORCINE PANCREATIC ELASTASE AND AC-ALA-PRO-VAL-2-BENZOXAZOLE
    EDWARDS, PD
    MEYER, EF
    VIJAYALAKSHMI, J
    TUTHILL, PA
    ANDISIK, DA
    GOMES, B
    STRIMPLER, A
    [J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1992, 114 (05) : 1854 - 1863