Synthesis and evaluation of prodrugs for anti-angiogenic pyrrolylmethylidenyl oxindoles

被引：47
作者：
Maskell, Lesley
Blanche, Emilie A.
Colucci, Marie A.
Whatmore, Jacqueline L.
Moody, Christopher J.
机构：
[1] Univ Exeter, Dept Chem, Exeter EX4 4AD, Devon, England
[2] Peninsula Med Sch, Exeter EX1 2LU, Devon, England
[3] Univ Nottingham, Sch Chem, Nottingham NG7 2RD, England
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2007年 / 17卷 / 06期
基金：
英国工程与自然科学研究理事会;
关键词：
oxindole; angiogenesis; prodrug; bioreduction;
D O I：
10.1016/j.bmcl.2006.12.108
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Potential prodrugs of inhibitors of VEGF-induced angiogenesis have been investigated. The prodrug systems studied were the 4-nitrobenzyl, 2-nitrophenylacetyl and 3-methyl-3-(3,6-dimethylbenzo-1,4-quinon-2-yl)butanoyI groups, readily attached to acidic OH or NH groups in drug molecules, and released upon bioreductive activation. The anti-angiogenic compounds studied were the pyrrolylmethylidenyl oxindole SU5416 (semaxanib) and its novel 6-hydroxy derivative. The potentially pro-anti-angiogenic compounds were assayed for their ability to block VEGF-induced angiogenesis in HUVECS in comparison to the free agents. (c) 2007 Elsevier Ltd. All rights reserved.
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收藏
页码：1575 / 1578
页数：4
相关论文
共 37 条
  • [1] AMINE PRODRUGS WHICH UTILIZE HYDROXY AMIDE LACTONIZATION .1. A POTENTIAL REDOX-SENSITIVE AMIDE PRODRUG
    AMSBERRY, KL
    BORCHARDT, RT
    [J]. PHARMACEUTICAL RESEARCH, 1991, 8 (03) : 323 - 330
  • [2] [Anonymous], ENZYME PRODRUG STRAT
  • [3] RELATIONSHIPS BETWEEN STRUCTURE AND KINETICS OF CYCLIZATION OF 2-AMINOARYL AMIDES - POTENTIAL PRODRUGS OF CYCLIZATION-ACTIVATED AROMATIC MUSTARDS
    ATWELL, GJ
    SYKES, BM
    OCONNOR, CJ
    DENNY, WA
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 1994, 37 (03) : 371 - 380
  • [4] SUBSTITUTED OXINDOLES .I. PREPARATION AND SPECTRAL CHARACTERISTICS OF SOME SIMPLE OXINDOLE DERIVATIVES
    BECKETT, AH
    DAISLEY, RW
    WALKER, J
    [J]. TETRAHEDRON, 1968, 24 (19) : 6093 - &
  • [5] Indolin-2-ones with high in vivo efficacy in a model for multiple sclerosis
    Bouérat, L
    Fensholdt, J
    Liang, XF
    Havez, S
    Nielsen, SF
    Hansen, JR
    Bolvig, S
    Andersson, C
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 2005, 48 (17) : 5412 - 5414
  • [6] REDUCTIVE LACTONIZATION OF STRATEGICALLY METHYLATED QUINONE PROPIONIC-ACID ESTERS AND AMIDES
    CARPINO, LA
    TRIOLO, SA
    BERGLUND, RA
    [J]. JOURNAL OF ORGANIC CHEMISTRY, 1989, 54 (14) : 3303 - 3310
  • [7] Regulation of VEGF/VPF expression in tumor cells: Consequences for tumor growth and metastasis
    Claffey, KP
    Robinson, GS
    [J]. CANCER AND METASTASIS REVIEWS, 1996, 15 (02) : 165 - 176
  • [8] A reinvestigation of the configuration of hemin
    Corwin, AH
    Krieble, RH
    [J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1941, 63 : 1829 - 1834
  • [9] Nitroreductase-based GDEPT
    Denny, WA
    [J]. CURRENT PHARMACEUTICAL DESIGN, 2002, 8 (15) : 1349 - 1361
  • [10] Novel phase I dose de-escalation design trial to determine the biological modulatory dose of the antiangiogenic agent SU5416
    Dowlati, A
    Robertson, K
    Radivoyevitch, T
    Waas, J
    Ziats, NP
    Hartman, P
    Abdul-Karim, FW
    Wasman, JK
    Jesberger, J
    Lewin, J
    McCrae, K
    Ivy, P
    Remick, SC
    [J]. CLINICAL CANCER RESEARCH, 2005, 11 (21) : 7938 - 7944
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