Design and synthesis of novel benzofurans as a new class of antifungal agents targeting fungal N-myristoyltransferase.: Part 1

被引:105
作者
Masubuchi, M [1 ]
Kawasaki, K [1 ]
Ebiike, H [1 ]
Ikeda, Y [1 ]
Tsujii, S [1 ]
Sogabe, S [1 ]
Fujii, T [1 ]
Sakata, K [1 ]
Shiratori, Y [1 ]
Aoki, Y [1 ]
Ohtsuka, T [1 ]
Shimma, N [1 ]
机构
[1] Nippon Roche Res Ctr, Kamakura, Kanagawa 2478530, Japan
关键词
D O I
10.1016/S0960-894X(01)00319-5
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Potent and selective Candida albicans N-myristoyltransferase (CaNmt) inhibitors have been identified through optimization of a lead compound 1 discovered by random screening. The inhibitor design is based on the crystal structure of the CaNmt complex with compound (S)-3 and structure-activity relationships (SARs) have been clarified. Modification of the C-4 side chain of 1 has led to thr discovery of a potent and selective CaNmt inhibitor 11 (RO-09-4609), which exhibits antifungal activity against C. albicans in vitro, (C) 2001 Elsevier Science Ltd. All rights reserved.
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页码:1833 / 1837
页数:5
相关论文
共 14 条
  • [1] AOKI Y, 1999, Patent No. 9763
  • [2] ATKINSON JG, 1985, Patent No. 146243
  • [3] Structure of N-myristoyltransferase with bound myristoylCoA and peptide substrate analogs
    Bhatnagar, RS
    Fütterer, K
    Farazi, TA
    Korolev, S
    Murray, CL
    Jackson-Machelski, E
    Gokel, GW
    Gordon, JI
    Waksman, G
    [J]. NATURE STRUCTURAL BIOLOGY, 1998, 5 (12) : 1091 - 1097
  • [4] Design and synthesis of novel imidazole-substituted dipeptide amides as potent and selective inhibitors of Candida albicans myristoylCoA:protein N-myristoyltransferase and identification of related tripeptide inhibitors with mechanism-based antifungal activity
    Devadas, B
    Freeman, SK
    Zupec, ME
    Lu, HF
    Nagarajan, SR
    Kishore, NS
    Lodge, JK
    Kuneman, DW
    McWherter, CA
    Vinjamoori, DV
    Getman, DP
    Gordon, JI
    Sikorski, JA
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 1997, 40 (16) : 2609 - 2625
  • [5] Novel biologically active nonpeptidic inhibitors of myristoylCoA:protein N-myristoyltransferase
    Devadas, B
    Freeman, SK
    McWherter, CA
    Kishore, NS
    Lodge, JK
    Jackson-Machelski, E
    Gordon, JI
    Sikorski, JA
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 1998, 41 (06) : 996 - 1000
  • [6] GORDON JI, 1991, J BIOL CHEM, V266, P8647
  • [7] GRINEV AN, 1986, Patent No. 772494901
  • [8] A NOVEL PROTEIN-KINASE HOMOLOG ESSENTIAL FOR PROTEIN SORTING TO THE YEAST LYSOSOME-LIKE VACUOLE
    HERMAN, PK
    STACK, JH
    DEMODENA, JA
    EMR, SD
    [J]. CELL, 1991, 64 (02) : 425 - 437
  • [9] GENETIC AND BIOCHEMICAL-STUDIES OF PROTEIN N-MYRISTOYLATION
    JOHNSON, DR
    BHATNAGAR, RS
    KNOLL, LJ
    GORDON, JI
    [J]. ANNUAL REVIEW OF BIOCHEMISTRY, 1994, 63 : 869 - 914
  • [10] TARGETED GENE REPLACEMENT DEMONSTRATES THAT MYRISTOYL-COA/PROTEIN N-MYRISTOYLTRANSFERASE IS ESSENTIAL FOR VIABILITY OF CRYPTOCOCCUS-NEOFORMANS
    LODGE, JK
    JACKSONMACHELSKI, E
    TOFFALETTI, DL
    PERFECT, JR
    GORDON, JI
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (25) : 12008 - 12012