G2 checkpoint inhibitors and assay

Details G2 checkpoint inhibitors and assay G2 checkpoint inhibitors and assay

C - Chemistry, Metallurgy

07

D

C07D 487/04 (2006.01) A61K 31/00 (2006.01) A61K 31/55 (2006.01) C07D 471/04 (2006.01) C07D 491/048 (2006.01) C07D 493/04 (2006.01) G01N 33/53 (2006.01) G01N 33/574 (2006.01)

Patent

CA 2216559

Compounds are provided that inhibit the G2 checkpoint in the cell cycle and are useful for sensitizing G1 deficient cancer cells to killing by DNA damaging agents. Also provided is an assay for G2 checkpoint inhibitors which includes applying a DNA damaging agent to p53 deficient cells and determining whether such cells do not arrest at G2 and proceed to mitosis after application of a sample to be tested. The assay may employ mitotic cell specific monoclonal antibodies. Compounds of this invention have the general formula: Image wherein R5 is selected from the group comprising: Image Image Image

Divulgation de composés qui inhibent le point de contrôle G2 dans le cycle cellulaire et qui sont utiles pour rendre les cellules cancéreuses se comportant de façon anormale en G1 vulnérables à l'action destructrice des agents qui endommagent l'ADN. Un dosage des inhibiteurs du point de contrôle G2 est également dévoilé; la méthode consiste à soumettre des cellules dont le gène p53 est amputé à l'action d'un agent endommageant l'ADN et à déterminer si ces cellules ne s'arrêtent pas à la phase G2 et procèdent à la mitose après application d'un échantillon d'essai. Le dosage peut employer des anticorps monoclonaux spécifiques des cellules mitotiques. Les composés dévoilés ont la formule générale : Image , dans laquelle R5 est choisi dans le groupe comprenant : Image Image Image .

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