7-[1H-indol-2-yl]-2,3-dihydro-isoindol-1-ones as dual Aurora-A/VEGF-R2 kinase inhibitors:: Design, synthesis, and biological activity

被引：22
|
作者：
Hughes, Terry V. [1 ]
Emanuel, Stuart L. [1 ]
O'Grady, Harold R. [1 ]
Connolly, Peter J. [1 ]
Rugg, Catherine [1 ]
Fuentes-Pesquera, Angel R. [1 ]
Karnachi, Prabha [1 ]
Alexander, Richard [1 ]
Middleton, Steven A. [1 ]
机构：
[1] Johnson & Johnson Pharmaceut Res & Dev LLC, Raritan, NJ 08869 USA
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2008年 / 18卷 / 18期
关键词：
cancer; Aurora-A; Aurora-B; Aurora-C; kinase; vascular endothelial growth factor receptor 2; VEGF-R2; kinase inhibition; isoindolinone; 2,3-dihydro-isoindol-1-ones;
D O I：
10.1016/j.bmcl.2008.07.090
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
A novel series of 7-[1H-indol-2-yl]-2,3-dihydro-isoindol-1-ones designed to be inhibitors of VEGF-R2 kinase was synthesized and found to potently inhibit VEGF-R2 and Aurora-A kinases. The structure-based design, synthesis, and initial SAR of the series are discussed. (C) 2008 Elsevier Ltd. All rights reserved.
引用
收藏
页码：5130 / 5133
页数：4
相关论文
共 50 条
  • [21] Design, synthesis and biological evaluation of dual Bcl-2/Mcl-1 inhibitors bearing 2-(1H-indol-4-yl)benzoic acid scaffold
    Niu, Qun
    Deng, Hongguang
    Zhang, Zhenwei
    Xu, Qinhao
    Luan, Shenglin
    Huang, Min
    Liu, Dan
    Zhao, Linxiang
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2021, 47
  • [22] Synthesis and Nootropic Activity of Some 2,3-Dihydro-1H-isoindol-1-one Derivatives Structurally Related with Piracetam
    Reyes, Adelfo
    Huerta, Leticia
    Alfaro, Marisol
    Navarrete, Andres
    CHEMISTRY & BIODIVERSITY, 2010, 7 (11) : 2718 - 2726
  • [23] Synthesis and biological evaluation of 3-ethylidene-1,3-dihydro-indol-2-ones as novel checkpoint 1 inhibitors
    Lin, NH
    Xia, P
    Kovar, P
    Park, C
    Chen, ZH
    Zhang, HY
    Rosenberg, SH
    Sham, HL
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2006, 16 (02) : 421 - 426
  • [24] 1,3-dihydro-2H-indol-2-ones derivatives: Design, Synthesis, in vitro antibacterial, antifungal and antitubercular study
    Akhaja, Tarunkumar Nanjibhai
    Raval, Jignesh Priyakant
    EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2011, 46 (11) : 5573 - 5579
  • [25] Multi-component Synthesis of 3-{3-[2-(1H-Indol-3-yl) ethyl]}-2,3-dihydro-2-(aryliminothiazol-4-yl)-2H-chromen-2-ones
    Aychiluhim, Tewodros Birhanu
    Rao, Vedula Rajeswar
    ORGANIC PREPARATIONS AND PROCEDURES INTERNATIONAL, 2014, 46 (01) : 66 - 75
  • [26] Synthesis of 2-(1,2,4-oxadiazol-5-yl)-2,3-dihydro-4H-chromen-4-ones
    Kysil, Andrii, I
    Biitseva, Angelina, V
    Bugera, Oleksandra, I
    Yegorova, Tetyana, V
    Voitenko, Zoia V.
    FRENCH-UKRAINIAN JOURNAL OF CHEMISTRY, 2020, 8 (02): : 176 - 182
  • [27] SYNTHESIS AND ANALGESIC ACTIVITY OF (2,3-DIPHENYL-1H-INDOL-5-YL)PIPERAZIN-1-YL METHANONE DERIVATIVES
    El-Nezhawy, A. O. H.
    El-Naem, S. I.
    Galal, S. A.
    El-Diwani, H. I.
    Salam, O. M. E. Abdel
    Baiomy, A. R.
    PHARMACEUTICAL CHEMISTRY JOURNAL, 2009, 43 (01) : 25 - 29
  • [28] Synthesis and analgesic activity of (2,3-diphenyl-1H-indol-5-YL)piperazin-1-yl methanone derivatives
    A. O. H. El-Nezhawy
    S. I. El-Naem
    S. A. Galal
    H. I. El-Diwani
    O. M. E. Abdel Salam
    A. R. Baiomy
    Pharmaceutical Chemistry Journal, 2009, 43 : 25 - 29
  • [29] Complementary Asymmetric Routes to (R)-2-(7-Hydroxy-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetate
    Schrader, Thomas O.
    Johnson, Benjamin R.
    Lopez, Luis
    Kasem, Michelle
    Gharbaoui, Tawfik
    Sengupta, Dipanjan
    Buzard, Daniel
    Basmadjian, Christine
    Jones, Robert M.
    ORGANIC LETTERS, 2012, 14 (24) : 6306 - 6309
  • [30] Synthesis and crystal structure of (3S)-3-(1H-benzotriazol-1-yl)- and (3S)-3-benzenesulfonyl-2-[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]-2,3-dihydro-1H-isoindol-1-ones
    Deniau, E
    Couture, A
    Grandclaudon, P
    Nowogrocki, G
    JOURNAL OF CHEMICAL RESEARCH-S, 2005, (05): : 319 - 321
12345