1403458-34-3Relevant academic research and scientific papers
Discovery of a series of 8-(1-phenylpyrrolidin-2-yl)-6-carboxamide-2-morpholino-4H-chromen-4-one as PI3Kβ/δ inhibitors for the treatment of PTEN-deficient tumours
Barlaam, Bernard,Cosulich, Sabina,Degorce, Sébastien,Ellston, Rebecca,Fitzek, Martina,Green, Stephen,Hancox, Urs,Lambert-van der Brempt, Christine,Lohmann, Jean-Jacques,Maudet, Micka?l,Morgentin, Rémy,Plé, Patrick,Ward, Lara,Warin, Nicolas
, p. 1949 - 1954 (2017/04/10)
Attempts to lock the active conformation of compound 4, a PI3Kβ/δ inhibitor (PI3Kβ cell IC50 0.015?μM), led to the discovery of a series of 8-(1-phenylpyrrolidin-2-yl)-6-carboxamide-2-morpholino-4H-chromen-4-ones, which showed high levels of potency and selectivity as PI3Kβ/δ inhibitors. Compound 10 proved exquisitely potent and selective: PI3Kβ cell IC50 0.0011?μM in PTEN null MDA-MB-468 cell and PI3Kδ cell IC50 0.014?μM in Jeko-1 B-cell, and exhibited suitable physical properties for oral administration. In vivo, compound 10 showed profound pharmacodynamic modulation of AKT phosphorylation in a mouse PTEN-null PC3 prostate tumour xenograft after a single oral dose and gave excellent tumour growth inhibition in the same model after chronic oral dosing. Based on these results, compound 10 was selected as one of our PI3Kβ/δ preclinical candidates.
CHROMENONE DERIVATIVES
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, (2012/10/23)
The invention concerns chromenone compounds of Formula I; or pharmaceutically-acceptable salts thereof, wherein each of R1, R2, R3, R4, R5, n and R6 has any of the meanings defined hereinbe
CHROMENONE COMPOUNDS AS PI 3 -KINASE INHIBITORS FOR THE TREATMENT OF CANCER
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, (2012/11/06)
The invention concerns chromenone compounds of Formula I; or pharmaceutically-acceptable salts thereof, wherein each of R1, R2, R3, R4, R5, n and R6 has any of the meanings defined hereinbe
