1034614-87-3Relevant academic research and scientific papers
NMS-P937, a 4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline derivative as potent and selective Polo-like kinase 1 inhibitor
Beria, Italo,Bossi, Roberto T.,Brasca, Maria Gabriella,Caruso, Michele,Ceccarelli, Walter,Fachin, Gabriele,Fasolini, Marina,Forte, Barbara,Fiorentini, Francesco,Pesenti, Enrico,Pezzetta, Daniele,Posteri, Helena,Scolaro, Alessandra,Depaolini, Stefania Re,Valsasina, Barbara
scheme or table, p. 2969 - 2974 (2011/06/24)
As part of our drug discovery effort, we identified and developed 4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline derivatives as PLK1 inhibitors. We now report the optimization of this class that led to the identification of NMS-P937, a potent, selective and orally available PLK1 inhibitor. Also, in order to understand the source of PLK1 selectivity, we determined the crystal structure of PLK1 with NMS-P937. The compound was active in vivo in HCT116 xenograft model after oral administration and is presently in Phase I clinical trials evaluation.
4,5-Dihydro-1H-pyrazolo[4,3-h]quinazolines as potent and selective Polo-like kinase 1 (PLK1) inhibitors
Beria, Italo,Valsasina, Barbara,Brasca, Maria Gabriella,Ceccarelli, Walter,Colombo, Maristella,Cribioli, Sabrina,Fachin, Gabriele,Ferguson, Ronald D.,Fiorentini, Francesco,Gianellini, Laura M.,Giorgini, Maria L.,Moll, Jurgen K.,Posteri, Helena,Pezzetta, Daniele,Roletto, Fulvia,Sola, Francesco,Tesei, Dania,Caruso, Michele
supporting information; experimental part, p. 6489 - 6494 (2011/01/12)
A series of 4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline derivatives was optimized as Polo-like kinase 1 inhibitors. Extensive SAR afforded a highly potent and selective PLK1 compound. The compound showed good antiproliferative activity when tested in a panel of tumor cell lines with PLK1 related mechanism of action and with good in vivo antitumor efficacy in two xenograft models after iv administration.
SUBSTITUTED PYRAZOLO-QUINAZOLINE DERIVATIVES, PROCESS FOR THEIR PREPARATION AND THEIR USE AS KINASE INHIBITORS
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Page/Page column 58; 61, (2008/12/06)
Pyrazolo-quinazoline derivatives of formula (I) as defined in the specification, and pharmaceutically acceptable salts thereof, process for their preparation and pharmaceutical compositions comprising them are disclosed; the compounds of the invention may
