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

P.G. Jagtap, E. Baloglu, G.J. Southan, Jon Mabley, H.S. Li, J. Zhou, J. van Duzer, A.L. Salzman, C. Szabo

Research output: Contribution to journalArticle

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 nonmutagenic 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
Pages (from-to)5100-5103
Number of pages4
JournalJournal of Medicinal Chemistry
Volume48
Issue number16
DOIs
Publication statusPublished - 16 Jul 2005

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