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 journalArticleResearch

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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Poly(ADP-ribose) Polymerases
Sulfonamides
Substitution reactions
Derivatives
Enzymes

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Jagtap, P.G. ; Baloglu, E. ; Southan, G.J. ; Mabley, Jon ; Li, H.S. ; Zhou, J. ; van Duzer, J. ; Salzman, A.L. ; Szabo, C. / Discovery of potent poly (ADP-ribose) polymerase-1 inhibitors from the modification of indeno[1,2-c]isoquinolinone. In: Journal of Medicinal Chemistry. 2005 ; Vol. 48, No. 16. pp. 5100-5103.
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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.",
author = "P.G. Jagtap and E. Baloglu and G.J. Southan and Jon Mabley and H.S. Li and J. Zhou and {van Duzer}, J. and A.L. Salzman and C. Szabo",
year = "2005",
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Jagtap, PG, Baloglu, E, Southan, GJ, Mabley, J, Li, HS, Zhou, J, van Duzer, J, Salzman, AL & Szabo, C 2005, 'Discovery of potent poly (ADP-ribose) polymerase-1 inhibitors from the modification of indeno[1,2-c]isoquinolinone', Journal of Medicinal Chemistry, vol. 48, no. 16, pp. 5100-5103. https://doi.org/10.1021/jm0502891

Discovery of potent poly (ADP-ribose) polymerase-1 inhibitors from the modification of indeno[1,2-c]isoquinolinone. / Jagtap, P.G.; Baloglu, E.; Southan, G.J.; Mabley, Jon; Li, H.S.; Zhou, J.; van Duzer, J.; Salzman, A.L.; Szabo, C.

In: Journal of Medicinal Chemistry, Vol. 48, No. 16, 16.07.2005, p. 5100-5103.

Research output: Contribution to journalArticleResearch

TY - JOUR

T1 - Discovery of potent poly (ADP-ribose) polymerase-1 inhibitors from the modification of indeno[1,2-c]isoquinolinone

AU - Jagtap, P.G.

AU - Baloglu, E.

AU - Southan, G.J.

AU - Mabley, Jon

AU - Li, H.S.

AU - Zhou, J.

AU - van Duzer, J.

AU - Salzman, A.L.

AU - Szabo, C.

PY - 2005/7/16

Y1 - 2005/7/16

N2 - 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.

AB - 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.

U2 - 10.1021/jm0502891

DO - 10.1021/jm0502891

M3 - Article

VL - 48

SP - 5100

EP - 5103

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

SN - 0022-2623

IS - 16

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