Karatas, Mehmet; Chaikuad, Apirat; Berger, Bianca; Kubbutat, Michael H. G.; Totzke, Frank; Knapp, Stefan; Kunick, Conrad published the artcile< 7-(2-Anilinopyrimidin-4-yl)-1-benzazepin-2-ones designed by a ""cut and glue"" strategy are dual Aurora A/VEGF-R kinase inhibitors>, Related Products of 25999-04-6, the main research area is anilinopyrimidinyl benzazepinone AuroraA VEGFR kinase inhibitor; Aurora kinase; X-ray structure analysis; anilinopyrimidine; benzazepinone; molecular docking; protein kinase inhibitor; sulfamide.
Although overexpression and hyperactivity of protein kinases are causative for a wide range of human cancers, protein kinase inhibitors currently approved as cancer drugs address only a limited number of these enzymes. To identify new chemotypes addressing alternative protein kinases, the basic structure of a known PLK1/VEGF-R2 inhibitor class was formally dissected and reassembled. The resulting 7-(2-anilinopyrimidin-4-yl)-1-benzazepin-2-ones were synthesized and proved to be dual inhibitors of Aurora A kinase and VEGF receptor kinases. Crystal structures of two representatives of the new chemotype in complex with Aurora A showed the ligand orientation in the ATP binding pocket and provided the basis for rational structural modifications. Congeners with attached sulfamide substituents retained Aurora A inhibitory activity. In vitro screening of two members of the new kinase inhibitor family against the cancer cell line panel of the National Cancer Institute (NCI) showed antiproliferative activity in the single-digit micromolar concentration range in the majority of the cell lines.
Molecules published new progress about Antiproliferative agents. 25999-04-6 belongs to class amides-buliding-blocks, and the molecular formula is C4H10N2O3S, Related Products of 25999-04-6.
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Amide – an overview | ScienceDirect Topics