1233339-96-2Relevant academic research and scientific papers
Discovery of 4-{4-[(3R)-3-methylmorpholin-4-yl]-6-[1-(methylsulfonyl) cyclopropyl]pyrimidin-2-yl}-1H-indole (AZ20): A potent and selective inhibitor of ATR protein kinase with monotherapy in vivo antitumor activity
Foote, Kevin M.,Blades, Kevin,Cronin, Anna,Fillery, Shaun,Guichard, Sylvie S.,Hassall, Lorraine,Hickson, Ian,Jacq, Xavier,Jewsbury, Philip J.,McGuire, Thomas M.,Nissink, J. Willem M.,Odedra, Rajesh,Page, Ken,Perkins, Paula,Suleman, Abid,Tam, Kin,Thommes, Pia,Broadhurst, Rebecca,Wood, Christine
supporting information, p. 2125 - 2138 (2013/05/09)
ATR is an attractive new anticancer drug target whose inhibitors have potential as chemo- or radiation sensitizers or as monotherapy in tumors addicted to particular DNA-repair pathways. We describe the discovery and synthesis of a series of sulfonylmorpholinopyrimidines that show potent and selective ATR inhibition. Optimization from a high quality screening hit within tight SAR space led to compound 6 (AZ20) which inhibits ATR immunoprecipitated from HeLa nuclear extracts with an IC50 of 5 nM and ATR mediated phosphorylation of Chk1 in HT29 colorectal adenocarcinoma tumor cells with an IC50 of 50 nM. Compound 6 potently inhibits the growth of LoVo colorectal adenocarcinoma tumor cells in vitro and has high free exposure in mouse following moderate oral doses. At well tolerated doses 6 leads to significant growth inhibition of LoVo xenografts grown in nude mice. Compound 6 is a useful compound to explore ATR pharmacology in vivo.
PYRIMIDINE INDOLE DERIVATIVES FOR TREATING CANCER
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Page/Page column 100, (2010/07/09)
There is provided pyrimidinyl indole compounds of Formula (I), or pharmaceutically acceptable salts thereof, processes for their preparation, pharmaceutical compositions containing them and their use in therapy, particularly for treating cancer.
