- CONDENSED PYRROLES AS NOVEL BROMODOMAIN INHIBITORS
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Compounds of formula (1) or (2) and their use in the treatment of diseases or conditions for which a bromodomain inhibitor is indicated.
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- 4-Acyl Pyrroles as Dual BET-BRD7/9 Bromodomain Inhibitors Address BETi Insensitive Human Cancer Cell Lines
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Various malignant human diseases show disturbed signaling pathways due to increased activity of proteins within the epigenetic machinery. Recently, various novel inhibitors for epigenetic regulation have been introduced which promise a great therapeutic benefit. Inhibitors for the bromo- and extra-terminal domain (BET) family were of particular interest after inhibitors had shown a strong antiproliferative effect. More recently, the focus has increasingly shifted to bromodomains (BDs) outside the BET family. Based on previously developed inhibitors, we have optimized a small series of 4-acyl pyrroles, which we further analyzed by ITC, X-ray crystallography, selectivity studies, the NCI60 cell-panel, and GI50 determinations for several cancer cell lines. The inhibitors address both, BET and BRD7/9 BDs, with very high affinity and show a strong antiproliferative effect on various cancer cell lines that could not be observed for BD family selective inhibitors. Furthermore, a synergistic effect on breast cancer (MCF-7) and melanoma (SK-MEL-5) was proven.
- Hügle, Martin,Regenass, Pierre,Warstat, Robin,Hau, Mirjam,Schmidtkunz, Karin,Lucas, Xavier,Wohlwend, Daniel,Einsle, Oliver,Jung, Manfred,Breit, Bernhard,Günther, Stefan
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p. 15603 - 15620
(2020/12/23)
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- Metallized phenyl-azo-naphthol compounds
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Metallized azo dyes of the formula STR1 wherein A is a sulfonyl, sulfonamido or carboxamido group, D is the residue of a phenol or naphthol, E is the residue of acetoacetanilide, a phenyl or naphthyl pyrazolone or the residue of a naphthol and M is a cation. The dyes are suitable for dyeing natural and synthetic polyamides, demonstrating good all-around fastness properties.
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- One step diazotization coupling process
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A process for producing metal-free azo pigments in purely organic liquid or aqueous/organic liquid containing at most 10% of water calculated on the total weight of the suspension is described. In this one-step process, a suitable aromatic amine is diazotized without isolation of the obtained diazo compound and coupled with a coupling component. Both reactions are carried out in purely or essentially organic medium. The latter consists essentially of such amount of an organic liquid that a substantial portion either of the diazo component or of the coupling component or of both these reactants remain undissolved. Both reactants must be free from sulphonic acid groups. If the resulting azo pigment contains carboxylic acid groups, these can be subsequently converted to the corresponding amido or ester groups.
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