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 Szabó

doi:10.1016/j.bmcl.2003.10.007

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 Szabó

Research output: Contribution to journal › Article › peer-review

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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 language	English (US)
Pages (from-to)	81-85
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	14
Issue number	1
DOIs	https://doi.org/10.1016/j.bmcl.2003.10.007
State	Published - Jan 5 2004
Externally published	Yes

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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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 IC 50 values of 45 and 100 nM, respectively.",

author = "Jagtap, {Prakash G.} and Southan, {Garry J.} and Erkan Baloglu and Siya Ram and Mabley, {Jon G.} and Anita Marton and Andrew Salzman and Csaba Szab{\'o}",

note = "Funding Information: This work was supported by grants from the National Institutes of Health (R44DK054099 and R44GM058986).",

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doi = "10.1016/j.bmcl.2003.10.007",

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AU - Jagtap, Prakash G.

AU - Southan, Garry J.

AU - Baloglu, Erkan

AU - Ram, Siya

AU - Mabley, Jon G.

AU - Marton, Anita

AU - Salzman, Andrew

AU - Szabó, Csaba

N1 - Funding Information: This work was supported by grants from the National Institutes of Health (R44DK054099 and R44GM058986).

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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 IC 50 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)

Abstract

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