Parp inhibitor compounds, compositions and methods of use

C - Chemistry – Metallurgy – 07 – D

Patent

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Details

C07D 487/06 (2006.01) A61K 31/517 (2006.01) A61K 31/551 (2006.01) A61K 31/635 (2006.01) A61P 35/00 (2006.01) C07D 519/00 (2006.01)

Patent

CA 2700903

The present invention relates to tetraaza phenalen-3-one compounds which inhibit poly (ADP-ribose) polymerase (PARP) and are useful in the chemosensitization of cancer therapeutics. The induction of peripheral neuropathy is a common side--effect of many of the conventional and newer chemotherapies. The present invention further provides means to reliably prevent or cure chemotherapy- induced neuropathy. The invention also relates to the use of the disclosed PARP inhibitor compounds in enhancing the efficacy of chemotherapeutic agents such as temozolomide. The invention also relates to the use of the disclosed PARP inhibitor compounds to radiosensitize tumor cells to ionizing radiation. The invention also relates to the use of the disclosed PARP inhibitor compounds for treatment of cancers with DNA repair defects.

La présente invention concerne des composés de tétra-azaphénalène-3-one qui inhibent la poly(ADP-ribose) polymérase (PARP) et se révèlent utiles pour la chimiosensibilisation lors d'un traitement anticancéreux. L'induction d'une neuropathie périphérique est un effet secondaire fréquent d'un grand nombre des chimiothérapies traditionnelles ou plus récentes. La présente invention concerne en outre des procédés de prévention ou de traitement efficaces d'une neuropathie induite par chimiothérapie. L'invention concerne également l'utilisation des composés inhibiteurs de la PARP pour le renforcement de l'efficacité des agents chimiothérapeutiques tels que le témozolomide. L'invention concerne également l'utilisation des composés inhibiteurs de la PARP pour la radiosensibilisation des cellules tumorales aux rayonnements ionisants. L'invention concerne encore l'utilisation des composés inhibiteurs de la PARP pour le traitement de cancers caractérisés par des défauts de réparation de l'ADN.

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