PARP-1 and PARP-2 are members of the family of poly(ADP-ribose) polymerases, which are involved in the maintenance of genomic integrity under conditions of genotoxic stimuli. The different roles of the two isoforms under pathophysiological conditions have not yet been fully clarified, and this is partially due to the lack of selective inhibitors. We report herein the synthesis and preliminary pharmacological evaluation of a large series of isoquinolinone derivatives as PARP-1/PARP-2 inhibitors. Among them, we identified the 5-benzoyloxyisoquinolin-1G(2H)-one derivative as the most selective PARP-2 inhibitor reported so far, with a PARP-2/PARP-1 selectivity indexgreater than 60.

On the way to selective PARP-2 inhibitors. Design, synthesis, and preliminary evaluation of a series of isoquinolinone derivatives / Pellicciari, R.; Costantino, Gabriele; Camaioni, E.; Formentini, L.; Sabbatini, P.; Venturoni, F.; Eren, G.; Bellocchi, D.; Chiarugi, A.; Moroni, F.. - In: CHEMMEDCHEM. - ISSN 1860-7179. - 3:(2008), pp. 914-923. [10.1002/cmdc.200800010]

On the way to selective PARP-2 inhibitors. Design, synthesis, and preliminary evaluation of a series of isoquinolinone derivatives

COSTANTINO, Gabriele;
2008-01-01

Abstract

PARP-1 and PARP-2 are members of the family of poly(ADP-ribose) polymerases, which are involved in the maintenance of genomic integrity under conditions of genotoxic stimuli. The different roles of the two isoforms under pathophysiological conditions have not yet been fully clarified, and this is partially due to the lack of selective inhibitors. We report herein the synthesis and preliminary pharmacological evaluation of a large series of isoquinolinone derivatives as PARP-1/PARP-2 inhibitors. Among them, we identified the 5-benzoyloxyisoquinolin-1G(2H)-one derivative as the most selective PARP-2 inhibitor reported so far, with a PARP-2/PARP-1 selectivity indexgreater than 60.
2008
On the way to selective PARP-2 inhibitors. Design, synthesis, and preliminary evaluation of a series of isoquinolinone derivatives / Pellicciari, R.; Costantino, Gabriele; Camaioni, E.; Formentini, L.; Sabbatini, P.; Venturoni, F.; Eren, G.; Bellocchi, D.; Chiarugi, A.; Moroni, F.. - In: CHEMMEDCHEM. - ISSN 1860-7179. - 3:(2008), pp. 914-923. [10.1002/cmdc.200800010]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/1833322
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