65399-17-9Relevant academic research and scientific papers
Structure-Based Design and Biological Characterization of Selective Histone Deacetylase 8 (HDAC8) Inhibitors with Anti-Neuroblastoma Activity
Heimburg, Tino,Kolbinger, Fiona R.,Zeyen, Patrik,Ghazy, Ehab,Herp, Daniel,Schmidtkunz, Karin,Melesina, Jelena,Shaik, Tajith Baba,Erdmann, Frank,Schmidt, Matthias,Romier, Christophe,Robaa, Dina,Witt, Olaf,Oehme, Ina,Jung, Manfred,Sippl, Wolfgang
, p. 10188 - 10204 (2018/01/10)
Histone deacetylases (HDACs) are important modulators of epigenetic gene regulation and additionally control the activity of non-histone protein substrates. While for HDACs 1-3 and 6 many potent selective inhibitors have been obtained, for other subtypes much less is known on selective inhibitors and the consequences of their inhibition. The present report describes the development of substituted benzhydroxamic acids as potent and selective HDAC8 inhibitors. Docking studies using available crystal structures have been used for structure-based optimization of this series of compounds. Within this study, we have investigated the role of HDAC8 in the proliferation of cancer cells and optimized hits for potency and selectivity, both in vitro and in cell culture. The combination of structure-based design, synthesis, and in vitro screening to cellular testing resulted in potent and selective HDAC8 inhibitors that showed anti-neuroblastoma activity in cellular testing.
Discovery of N-(3-(morpholinomethyl)-phenyl)-amides as potent and selective CB2 agonists
Worm, Karin,Weaver, Damian G.,Green, Rosalyn C.,Saeui, Christopher T.,Dulay, Doreen-Marie S.,Barker, William M.,Cassel, Joel A.,Stabley, Gabriel J.,DeHaven, Robert N.,LaBuda, Christopher J.,Koblish, Michael,Brogdon, Bernice L.,Smith, Steven A.,Dolle, Roland E.
scheme or table, p. 5004 - 5008 (2010/03/24)
Recently sulfamoyl benzamides were identified as a novel series of cannabinoid receptor ligands. Replacing the sulfonamide functionality and reversing the original carboxamide bond led to the discovery of N-(3-(morpholinomethyl)-phenyl)-amides as potent and selective CB2 agonists. Selective CB2 agonist 31 (Ki = 2.7; CB1/CB2 = 190) displayed robust activity in a rodent model of postoperative pain.
Discovery of a potent and selective c-Kit inhibitor for the treatment of inflammatory diseases
Chen, Ning,Buerli, Roland W.,Neira, Susana,Hungate, Randall,Zhang, Dawei,Yu, Violeta,Nguyen, Yen,Tudor, Yanyan,Plant, Matthew,Flynn, Shaun,Meagher, Kristin L.,Lee, Matthew R.,Zhang, Xuxia,Itano, Andrea,Schrag, Michael,Xu, Yang,Ng, Gordon Y.,Hu, Essa
scheme or table, p. 4137 - 4141 (2009/05/26)
A potent and selective c-Kit inhibitor 20 was identified through a structure-activity relationship study. In an in vivo mouse model of mast cell activation, 20 blocked the SCF-induced histamine release with an EC50 of 26 nM.
NOVEL TRIAZOLOPYRIDINE COMPOUNDS
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Page/Page column 79; 80, (2008/06/13)
This invention is directed generally to triazolopyridine compounds that generally inhibit p38 kinase, TNF, and/or cyclooxygenase activity. Such triazolopyridine include compounds generally corresponding in structure to the following formula (I): wherein R
NOVEL TRIAZOLOPYRIDINE COMPOUNDS FOR THE TREATMENT OF INFLAMMATION
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Page/Page column 95-96, (2008/06/13)
This invention is directed generally to triazolopyridine compounds that generally inhibit p38 kinase, TNF, and/or cyclooxygenase activity. Such triazolopyridine include compounds generally corresponding in structure to the following formula (I): Wherein R1, R2, R3, R4, and R5are as defined in this specification. This invention also is directed to compositions of such triazolopyridines (particularly pharmaceutical compositions), intermediates for the syntheses of such triazolopyridines, methods for making such triazolopyridines, and methods for treating (including preventing) conditions (typically pathological conditions) associated with p38 kinase activity, TNF activity, and/or cyclooxygenase-2 activity.
