Discovery of potent poly(ADP-ribose) polymerase-1 inhibitors from the modification of indeno[1,2-c]isoquinolinone

Prakash G. Jagtap, Erkan Baloglu, Garry J. Southan, Jon G. Mabley, Hongshan Li, Jing Zhou, John Van Duzer, Andrew L. Salzman, Csaba Szabó

    Research output: Contribution to journalArticlepeer-review

    73 Scopus citations

    Abstract

    Novel indeno[1,2-c]isoquinolinone derivatives were synthesized and evaluated as inhibitors of the nuclear enzyme poly(ADP-ribose) polymerase-1 (PARP-1). These potent non-mutagenic PARP-1 inhibitors possess an additional five-membered ring between the B and C rings of 6(5H)-phenanthridinone. The most potent PARP-1 inhibitors were obtained from the substitution of the D ring at the C-9 position, in particular sulfonamide and N-acyl analogues (6 and 11). The 9-sulfonamide analogues 11a and 12a exhibited IC50 values of 1 and 10 nM, respectively.

    Original languageEnglish (US)
    Pages (from-to)5100-5103
    Number of pages4
    JournalJournal of medicinal chemistry
    Volume48
    Issue number16
    DOIs
    StatePublished - Aug 11 2005

    ASJC Scopus subject areas

    • Molecular Medicine
    • Drug Discovery

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