Most of the compounds have physiologically active properties, and their biological properties are often attributed to the heteroatoms contained in their molecules, and most of these heteroatoms also appear in cyclic structures. A Journal, Article, European Journal of Medicinal Chemistry called Pyrido[2,3-b][1,5]benzoxazepin-5(6H)-one derivatives as CDK8 inhibitors, Author is Martinez-Gonzalez, Sonia; Garcia, Ana Belen; Albarran, M. Isabel; Cebria, Antonio; Amezquita-Alves, Adrian; Garcia-Campos, Francisco Javier; Martinez-Gago, Jaime; Martinez-Torrecuadrada, Jorge; Munoz, Ines; Blanco-Aparicio, Carmen; Pastor, Joaquin, which mentions a compound: 49609-84-9, SMILESS is O=C(Cl)C1=CC=CN=C1Cl, Molecular C6H3Cl2NO, Application of 49609-84-9.
CDK8 is a cyclin-dependent kinase that forms part of the mediator complex, and modulates the transcriptional output from distinct transcription factors involved in oncogenic control. Overexpression of CDK8 has been observed in various cancers, representing a potential target for developing novel CDK8 inhibitors in cancer therapeutics. In the course of our investigations to discover new CDK8 inhibitors, we designed and synthesized tricyclic pyrido[2,3-b][1,5]benzoxazepin-5(6H)-one derivatives, by introduction of chem. complexity in the multi-kinase inhibitor Sorafenib taking into account the flexibility of the P-loop motif of CDK8 protein observed after anal. of structural information of co-crystallized CDK8 inhibitors. In vitro evaluation of the inhibitory activity of the prepared compounds against CDK8 led us to identify compound I as the most potent inhibitor of the series (IC50 = 8.25 nM). Co-crystal studies and the remarkable selectivity profile of compound I are presented. Compound I showed moderate reduction of phosphorylation of CDK8 substrate STAT1 in cells, in line with other reported Type II CDK8 inhibitors. We propose herein an alternative to find a potential therapeutic use for this chem. series.
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Phosphine ligand,
Chiral phosphine ligands in asymmetric synthesis. Molecular structure and absolute configuration of (1,5-cyclooctadiene)-(2S,3S)-2,3-bis(diphenylphosphino)butanerhodium(I) perchlorate tetrahydrofuran solvate