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)

P. Jagtap, G.J. Southan, E. Baloglu, E. Ram, Jon Mabley, A. Marton, A.L. Salzman, C. Szabo

Research output: Contribution to journalArticle

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 IC50 values of 45 and 100 nM, respectively.
Original languageEnglish
Pages (from-to)81-85
Number of pages5
JournalBioorganic & Medicinal Chemistry Letters
Volume14
DOIs
Publication statusPublished - Jan 2004

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