Design and Synthesis of Two Cytotoxic Analogs of the Novel Pyrrolo[1', 2':1, 2][1, 4]diazepin [7, 6-b]indol-5(6H)-one Nucleus

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著者

    • TSOTINIS Andrew
    • University of Athens, School of Pharmacy, Department of Pharmaceutical Chemistry, Panepistimiopolis-Zografou
    • VLACHOU Margarita
    • University of Athens, School of Pharmacy, Department of Pharmaceutical Chemistry, Panepistimiopolis-Zografou
    • KIAKOS Konstantinos
    • CR-UK Gene Targeted Drug Design Research Group, The School of Pharmacy, University of London
    • HARTLEY John A.
    • CR-UK Drug-DNA Interactions Research Group, Department of Oncology, Royal Free & University College Medical School, UCL
    • THURSTON David E.
    • CR-UK Gene Targeted Drug Design Research Group, The School of Pharmacy, University of London

抄録

The design and synthesis of the two cytotoxic derivatives <B>15</B> and <B>16</B> of the novel pyrrolo[1′,2′:1,2][1,4]diazepin[7,6-<I>b</I>]indol-5(6<I>H</I>)-one nucleus is described. Readily available methyl 2-indolecarboxylates <B>5</B> and <B>6</B> are nitrosated with NaNO<SUB>2</SUB> in AcOH to give the analogs <B>7</B> and <B>8</B>, which are then oxidized with KMnO<SUB>4</SUB> in aq. NaOH to provide the 3-NO<SUB>2</SUB> acids <B>9</B> and <B>10</B>. These, in turn, are subjected to amidation with (2<I>S</I>)-pyrrolidine-2-carboxaldehyde diethyl thioacetal in the presence of EDCI and HOBt and then to a 7-<I>exo</I>-trig cyclization reaction to give the target molecules <B>15</B> and <B>16</B>. The new analogs were evaluated in the human leukemic K<SUB>562</SUB> cell line and were shown to have micromolar potency.

収録刊行物

  • Chemistry letters

    Chemistry letters 32(6), 512-513, 2003-06-05

    The Chemical Society of Japan

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各種コード

  • NII論文ID(NAID)
    10012816792
  • NII書誌ID(NCID)
    AA00603318
  • 本文言語コード
    ENG
  • 資料種別
    SHO
  • ISSN
    03667022
  • データ提供元
    CJP書誌  J-STAGE 
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