Synthesis of 7-alkylidene-7,12-dihydroindolo(3,2-d)benzazepine-6-(5H)-ones (7-alkylidene-paullones) by N-cyclization oxidative Heck cascade and characterization as sirtuin modulators

被引：24
作者：
Denis, J. G. [1 ,2 ]
Franci, G. [3 ]
Altucci, L. [3 ]
Aurrecoechea, J. M. [4 ]
de Lera, A. R. [1 ,2 ]
Alvarez, R. [1 ,2 ]
机构：
[1] Univ Vigo, Dept Quim Organ, Fac Quim CINBIO, Vigo 36310, Spain
[2] Univ Vigo, Inst Invest Biomed Vigo IBIV, Vigo 36310, Spain
[3] Univ Naples 2, Dipartimento Biochim Biofis & Patol Gen, I-80138 Naples, Italy
[4] Univ Basque Country, Dept Quim Organ 2, Fac Ciencia & Tecnol, E-48080 Bilbao, Spain
来源：
ORGANIC & BIOMOLECULAR CHEMISTRY | 2015年 / 13卷 / 09期
关键词：
KINASE INHIBITORS; PAULLONES; INDOLES; ACTIVATION; ANALOGS; CORE;
D O I：
10.1039/c4ob02493a
中图分类号：
O62 [有机化学];
学科分类号：
070303 ; 081704 ;
摘要：
An extension of our reported protocol to benzofused heterocyclic derivatives (benzofurans, indoles, isochromeneimines), involving a palladium-induced cascade of N-cyclization and oxidative Heck reactions of o-alkynylanilines, has allowed the preparation of indolobenzazepinones (paullones) with an alkylidene group at C7 in just 3-4 steps from ortho-iodoanilines. Some of these compounds behave as Sirt1 activators in biochemical assays.
引用
收藏
页码：2800 / 2810
页数：11
相关论文
共 53 条
  • [1] A General Synthesis of Alkenyl-Substituted Benzofurans, Indoles, and Isoquinolones by Cascade Palladium-Catalyzed Heterocyclization/Oxidative Heck Coupling
    Alvarez, Rosana
    Martinez, Claudio
    Madich, Youssef
    Denis, J. Gabriel
    Aurrecoechea, Jose M.
    de Lera, Angel R.
    [J]. CHEMISTRY-A EUROPEAN JOURNAL, 2010, 16 (42) : 12746 - 12753
  • [2] Structure of a Sir2 enzyme bound to an acetylated p53 peptide
    Avalos, JL
    Celic, I
    Muhammad, S
    Cosgrove, MS
    Boeke, JD
    Wolberger, C
    [J]. MOLECULAR CELL, 2002, 10 (03) : 523 - 535
  • [3] New Heck coupling strategies for the synthesis of paullone and dimethyl paullone
    Avila-Zarraga, Jose Gustavo
    Lujan-Montelongo, Armando
    Covarrubias-Zuniga, Adrian
    Romero-Ortega, Moises
    [J]. TETRAHEDRON LETTERS, 2006, 47 (45) : 7987 - 7989
  • [4] Application of the palladium-catalyzed borylation/Suzuki coupling (BSC) reaction to the synthesis of biologically active biaryl lactams
    Baudoin, O
    Cesario, M
    Guénard, D
    Guéritte, F
    [J]. JOURNAL OF ORGANIC CHEMISTRY, 2002, 67 (04) : 1199 - 1207
  • [5] Development of 5-benzylpaullones and paullone-9-carboxylic acid alkyl esters as selective inhibitors of mitochondrial malate dehydrogenase (mMDH)
    Becker, Anja
    Kohfeld, Simone
    Lader, Annette
    Preu, Lutz
    Pies, Tanja
    Wieking, Karen
    Ferandin, Yoan
    Knockaert, Marie
    Meijer, Laurent
    Kunick, Conrad
    [J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2010, 45 (01) : 335 - 342
  • [6] The heck reaction as a sharpening stone of palladium catalysis
    Beletskaya, IP
    Cheprakov, AV
    [J]. CHEMICAL REVIEWS, 2000, 100 (08) : 3009 - 3066
  • [7] An iodoacetamide-based free radical cyclisation approach to the 7,12-dihydro-indolo[3,2-d] [1]benzazepin-6(5H)-one (paullone) system
    Bremner, JB
    Sengpracha, W
    [J]. TETRAHEDRON, 2005, 61 (23) : 5489 - 5498
  • [8] Small-Molecule Suppressors of Cytokine-Induced β-Cell Apoptosis
    Chou, Danny Hung-Chieh
    Bodycombe, Nicole E.
    Carrinski, Hyman A.
    Lewis, Timothy A.
    Clemons, Paul A.
    Schreiber, Stuart L.
    Wagner, Bridget K.
    [J]. ACS CHEMICAL BIOLOGY, 2010, 5 (08) : 729 - 734
  • [9] A highly cytotoxic modified paullone ligand bearing a TEMPO free-radical unit and its copper(II) complex as potential hR2 RNR inhibitors
    Dobrov, Anatolie
    Goeschl, Simone
    Jakupec, Michael A.
    Popovic-Bijelic, Ana
    Graslund, Astrid
    Rapta, Peter
    Arion, Vladimir B.
    [J]. CHEMICAL COMMUNICATIONS, 2013, 49 (85) : 10007 - 10009
  • [10] Identification of 2-Anilino-9-methoxy-5,7-dihydro-6H-pyrimido[5,4-d][1]benzazepin-6-ones as Dual PLK1/VEGF-R2 Kinase Inhibitor Chemotypes by Structure-Based Lead Generation
    Egert-Schmidt, Anne-Marie
    Dreher, Jan
    Dunkel, Ute
    Kohfeld, Simone
    Preu, Lutz
    Weber, Holger
    Ehlert, Jan E.
    Mutschler, Bettina
    Totzke, Frank
    Schaechtele, Christoph
    Kubbutat, Michael H. G.
    Baumann, Knut
    Kunick, Conrad
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 2010, 53 (06) : 2433 - 2442
123456