1086111-09-2Relevant articles and documents
Convergent and Practical Synthesis of Fluorescent Triphenylamine Derivatives and Their Localization in Living Cells
Auvray, Marie,Franck, Xavier,Gallavardin, Thibault,Leleu, Stéphane,Mahuteau-Betzer, Florence,Mougeot, Romain,Oger, Samuel
supporting information, (2022/02/09)
In the search for new fluorescent triphenylamine (TP) derivatives, we studied the influence of the position and substitution of diverse heterocyclic substituents. A library of 10 fluorescent triphenylamines bearing either oxazoles or thiazoles and pyridiniums, substituted at different positions has been developed. The approach is based on a convergent C?H activation reaction between pyridine-oxazoles or pyridine-thiazoles and di-iodo triphenylamine. We showed that the nature and substitution pattern of the 5-membered- (oxazole, thiazole) or 6-membered heterocycle (pyridine) has a strong influence on their fluorescence properties and on their localization in living cells as they stain either the nucleus or mitochondria.
Mitigation of Acetylcholine Esterase Activity in the 1,7-Diazacarbazole Series of Inhibitors of Checkpoint Kinase 1
Gazzard, Lewis,Williams, Karen,Chen, Huifen,Axford, Lorraine,Blackwood, Elizabeth,Burton, Brenda,Chapman, Kerry,Crackett, Peter,Drobnick, Joy,Ellwood, Charles,Epler, Jennifer,Flagella, Michael,Gancia, Emanuela,Gill, Matthew,Goodacre, Simon,Halladay, Jason,Hewitt, Joanne,Hunt, Hazel,Kintz, Samuel,Lyssikatos, Joseph,Macleod, Calum,Major, Sarah,Médard, Guillaume,Narukulla, Raman,Ramiscal, Judi,Schmidt, Stephen,Seward, Eileen,Wiesmann, Christian,Wu, Ping,Yee, Sharon,Yen, Ivana,Malek, Shiva
, p. 5053 - 5074 (2015/07/02)
Checkpoint kinase 1 (ChK1) plays a key role in the DNA damage response, facilitating cell-cycle arrest to provide sufficient time for lesion repair. This leads to the hypothesis that inhibition of ChK1 might enhance the effectiveness of DNA-damaging therapies in the treatment of cancer. Lead compound 1 (GNE-783), the prototype of the 1,7-diazacarbazole class of ChK1 inhibitors, was found to be a highly potent inhibitor of acetylcholine esterase (AChE) and unsuitable for development. A campaign of analogue synthesis established SAR delineating ChK1 and AChE activities and allowing identification of new leads with improved profiles. In silico docking using a model of AChE permitted rationalization of the observed SAR. Compounds 19 (GNE-900) and 30 (GNE-145) were identified as selective, orally bioavailable ChK1 inhibitors offering excellent in vitro potency with significantly reduced AChE activity. In combination with gemcitabine, these compounds demonstrate an in vivo pharmacodynamic effect and are efficacious in a mouse p53 mutant xenograft model.
DIAZACARBAZOLES AND METHODS OF USE
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Page/Page column 167, (2010/01/07)
The invention relates to 1,7-diazacarbazole compounds of Formula (I), (I-a) and (I-b) which are useful as kinase inhibitors, more specifically useful as checkpoint kinase 1 (chkl) inhibitors, thus useful as cancer therapeutics. The invention also relates to compositions, more specifically pharmaceutical compositions comprising these compounds and methods of using the same to treat various forms of cancer and hyperproliferative disorders, as well as methods of using the compounds for in vitro, in situ, and in vivo diagnosis or treatment of mammalian cells, or associated pathological conditions.