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 Szabo

Research output: Contribution to journalArticle

57 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Adenosine
Poly(ADP-ribose) Polymerases
Derivatives
Poly(ADP-ribose) Polymerase Inhibitors
1-oxoisoindole
Poly (ADP-Ribose) Polymerase-1
piperazine

ASJC Scopus subject areas

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

Cite this

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). / Jagtap, Prakash G.; Southan, Garry J.; Baloglu, Erkan; Ram, Siya; Mabley, Jon G.; Marton, Anita; Salzman, Andrew; Szabo, Csaba.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 14, No. 1, 05.01.2004, p. 81-85.

Research output: Contribution to journalArticle

Jagtap, Prakash G. ; Southan, Garry J. ; Baloglu, Erkan ; Ram, Siya ; Mabley, Jon G. ; Marton, Anita ; Salzman, Andrew ; Szabo, Csaba. / 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). In: Bioorganic and Medicinal Chemistry Letters. 2004 ; Vol. 14, No. 1. pp. 81-85.
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