4-[3-(4-cyclopropanecarbonylpiperazine-1-carbonyl)-4-fluorobenzyl]-2 H-phthalazin-1-one: a novel bioavailable inhibitor of poly (ADP-ribose) polymerase-1

…, H Javaid, F Kerrigan, C Knights, A Lau…

Index: Menear, Keith A.; Adcock, Claire; Boulter, Robert; Cockcroft, Xiao-Ling; Copsey, Louise; Cranston, Aaron; Dillon, Krystyna J.; Drzewiecki, Jan; Garman, Sheila; Gomez, Sylvie; Javaid, Hashim; Kerrigan, Frank; Knights, Charlotte; Lau, Alan; Loh Jr., Vincent M.; Matthews, Ian T. W.; Moore, Stephen; O'Connor, Mark J.; Smith, Graeme C. M.; Martin, Niall M. B. Journal of Medicinal Chemistry, 2008 , vol. 51, # 20 p. 6581 - 6591

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Citation Number: 268

Abstract

Poly (ADP-ribose) polymerase activation is an immediate cellular response to metabolic-, chemical-, or ionizing radiation-induced DNA damage and represents a new target for cancer therapy. In this article, we disclose a novel series of substituted 4-benzyl-2 H- phthalazin-1-ones that possess high inhibitory enzyme and cellular potency for both PARP-1 and PARP-2. Optimized compounds from the series also demonstrate good ...