545394-33-0Relevant academic research and scientific papers
Potent and Selective Inhibitors of 8-Oxoguanine DNA Glycosylase
Tahara, Yu-Ki,Auld, Douglas,Ji, Debin,Beharry, Andrew A.,Kietrys, Anna M.,Wilson, David L.,Jimenez, Marta,King, Daniel,Nguyen, Zachary,Kool, Eric T.
, p. 2105 - 2114 (2018/02/19)
The activity of DNA repair enzyme 8-oxoguanine DNA glycosylase (OGG1), which excises oxidized base 8-oxoguanine (8-OG) from DNA, is closely linked to mutagenesis, genotoxicity, cancer, and inflammation. To test the roles of OGG1-mediated repair in these pathways, we have undertaken the development of noncovalent small-molecule inhibitors of the enzyme. Screening of a PubChem-annotated library using a recently developed fluorogenic 8-OG excision assay resulted in multiple validated hit structures, including selected lead hit tetrahydroquinoline 1 (IC50 = 1.7 μM). Optimization of the tetrahydroquinoline scaffold over five regions of the structure ultimately yielded amidobiphenyl compound 41 (SU0268; IC50 = 0.059 μM). SU0268 was confirmed by surface plasmon resonance studies to bind the enzyme both in the absence and in the presence of DNA. The compound SU0268 was shown to be selective for inhibiting OGG1 over multiple repair enzymes, including other base excision repair enzymes, and displayed no toxicity in two human cell lines at 10 μM. Finally, experiments confirm the ability of SU0268 to inhibit OGG1 in HeLa cells, resulting in an increase in accumulation of 8-OG in DNA. The results suggest the compound SU0268 as a potentially useful tool in studies of the role of OGG1 in multiple disease-related pathways.
A versatile route to red-emitting carbopyronine dyes for optical microscopy and nanoscopy
Kolmakov, Kirill,Belov, Vladimir N.,Wurm, Christian A.,Harke, Benjamin,Leutenegger, Marcel,Eggeling, Christian,Hell, Stefan W.
supporting information; experimental part, p. 3593 - 3610 (2010/11/18)
Biological microscopy favors photostable fluorescent markers with large fluorescence quantum yields, low dark triplet state population, good biocompatibility and absorption and emission maxima in the near-infrared, where cellular autofluorescence is minimized. In the present study, carbopyronines absorbing around 640 nm and emitting at around 660 nm, with a low intersystem crossing rate (kisc ≈ 0.5×106 s-1) and excellent properties for cellular imaging were synthesized. A general synthetic route to carbopyronines with functional groups variable in the final steps of the synthesis or in the resulting fluorescent dye is presented. Possessing two 2-me-thoxyethyl groups, the parent dye is soluble in water and most organic solvents. Demethylation of the dye or its precursors is straightforward, clean, and furnishes compounds with one or two 2-hydroxyethyl groups, which can be used for further transformations. Modifications in the linker-containing carboxy group are also possible. A multistep synthesis of the dye starting from a simple precursor and utilizing a single temporary protective group is described. The presented approach may be further applied to the design of caged carbopyronines.
PYRAZOLE PYRAZINE AMINE COMPOUNDS AS KINASE INHIBITORS, COMPOSITIONS THEREOF AND METHODS OF TREATMENT THEREWITH
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Page/Page column 130, (2009/09/04)
Provided herein are Pyrazole Pyrazine Amine Compounds having the following structure:Formula (I). Wherein Q and R1-R3 are as defined herein, compositions comprising an effective amount of a Pyrazole Pyrazine Amine Compound and methods for treating or preventing inflammatory conditions, immunological conditions, cancer, neurodegenerative diseases, age-related diseases, cardiovascular diseases and metabolic conditions, or conditions treatable or preventable by inhibition of an IKK, or an IKK pathway, comprising administering an effective amount of a Pyrazole Pyrazine Amine Compound to a patient in need thereof.
Vanilloid receptor ligands and their use in treatments
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, (2008/06/13)
Compounds having the general structure and compositions containing them, for the treatment of acute, inflammatory and neuropathic pain, dental pain, general headache, migraine, cluster headache, mixed-vascular and non-vascular syndromes, tension headache, general inflammation, arthritis, rheumatic diseases, osteoarthritis, inflammatory bowel disorders, inflammatory eye disorders, inflammatory or unstable bladder disorders, psoriasis, skin complaints with inflammatory components, chronic inflammatory conditions, inflammatory pain and associated hyperalgesia and allodynia, neuropathic pain and associated hyperalgesia and allodynia, diabetic neuropathy pain, causalgia, sympathetically maintained pain, deafferentation syndromes, asthma, epithelial tissue damage or dysfunction, herpes simplex, disturbances of visceral motility at respiratory, genitourinary, gastrointestinal or vascular regions, wounds, burns, allergic skin reactions, pruritis, vitiligo, general gastrointestinal disorders, gastric ulceration, duodenal ulcers, diarrhea, gastric lesions induced by necrotising agents, hair growth, vasomotor or allergic rhinitis, bronchial disorders or bladder disorders.
