Discovery of (naphthalen-4-yl)( phenyl) methanones and N-methyl-N-phenylnaphthalen-1-amines as new apoptosis inducers using a cell- and caspase-based HTS assay

[摘要]：We report the discovery of a series of (naphthalen-4-yl)(phenyl)methanones as potent inducers of apoptosis using our proprietary cell- and caspase-based ASAP HTS assay. Through SAR studies, a group of N-methyl-N-phenylnaphthalen-1-amines also were identified as potent inducers of apoptosis. (1-(Dimethylamino) naphthalen-4-yl)(4-(dimethylamino)phenyl)methanone (2a), one of the most potent analogs, had EC50 values of 37, 49 and 44 nM in T47D, HCT116 and SNU398 cells, respectively. Compound 2a also was highly active in a growth inhibition assay with an GI(50) value of 34 nM in T47D cells. Functionally, compound 2a arrested HCT116 cells in G(2)/M followed by induction of apoptosis and inhibited tubulin polymerization. (C) 2008 Elsevier Ltd. All rights reserved.

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