The discovery and synthesis of novel adenosine substituted 2,3-dihydro-1H-isoindol-1-ones: Potent inhibitors of poly(ADP-ribose) polymerase-1 (PARP-1)

Prakash G. Jagtap, Garry J. Southan, Erkan Baloglu, Siya Ram, Jon G. Mabley, Anita Marton, Andrew Salzman, Csaba Szabó

    Research output: Contribution to journalArticle

    61 Scopus citations

    Abstract

    A series of novel 4-(N-acyl)-2,3-dihydro-1H-isoindol-1-ones have been prepared from methyl-3-nitro-2-methylbenzoate and linked through various spacers to the adenosine derivatives 11 and 12. We found that potent inhibition of poly(ADP-ribose)polymerase-1 (PARP-1) was achieved when isoindolinone was linked to adenosine by a spacer group of a specific length. Introduction of piperazine and succinyl linkers between the isoindolinone and adenosine core structures resulted in highly potent compounds 8a and 10b, which showed IC 50 values of 45 and 100 nM, respectively.

    Original languageEnglish (US)
    Pages (from-to)81-85
    Number of pages5
    JournalBioorganic and Medicinal Chemistry Letters
    Volume14
    Issue number1
    DOIs
    StatePublished - Jan 5 2004

    ASJC Scopus subject areas

    • Biochemistry
    • Molecular Medicine
    • Molecular Biology
    • Pharmaceutical Science
    • Drug Discovery
    • Clinical Biochemistry
    • Organic Chemistry

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