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 journalArticleResearchpeer-review

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

Cite this

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title = "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)",
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.",
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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, P.; Southan, G.J.; Baloglu, E.; Ram, E.; Mabley, Jon; Marton, A.; Salzman, A.L.; Szabo, C.

In: Bioorganic & Medicinal Chemistry Letters, Vol. 14, 01.2004, p. 81-85.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - 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)

AU - Jagtap, P.

AU - Southan, G.J.

AU - Baloglu, E.

AU - Ram, E.

AU - Mabley, Jon

AU - Marton, A.

AU - Salzman, A.L.

AU - Szabo, C.

PY - 2004/1

Y1 - 2004/1

N2 - 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.

AB - 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.

U2 - 10.1016/j.bmcl.2003.10.007

DO - 10.1016/j.bmcl.2003.10.007

M3 - Article

VL - 14

SP - 81

EP - 85

JO - Bioorganic & Medicinal Chemistry Letters

JF - Bioorganic & Medicinal Chemistry Letters

SN - 0960-894X

ER -