331963-40-7Relevant academic research and scientific papers
Subtly Modulating Glycogen Synthase Kinase 3 β: Allosteric Inhibitor Development and Their Potential for the Treatment of Chronic Diseases
Palomo, Valle,Perez, Daniel I.,Roca, Carlos,Anderson, Cara,Rodríguez-Muela, Natalia,Perez, Concepción,Morales-Garcia, Jose A.,Reyes, Julio A.,Campillo, Nuria E.,Perez-Castillo, Ana M.,Rubin, Lee L.,Timchenko, Lubov,Gil, Carmen,Martinez, Ana
, p. 4983 - 5001 (2017/06/28)
Glycogen synthase kinase 3 β (GSK-3β) is a central target in several unmet diseases. To increase the specificity of GSK-3β inhibitors in chronic treatments, we developed small molecules allowing subtle modulation of GSK-3β activity. Design synthesis, structure-Activity relationships, and binding mode of quinoline-3-carbohydrazide derivatives as allosteric modulators of GSK-3β are presented here. Furthermore, we show how allosteric binders may overcome the β-catenin side effects associated with strong GSK-3β inhibition. The therapeutic potential of some of these modulators has been tested in human samples from patients with congenital myotonic dystrophy type 1 (CDM1) and spinal muscular atrophy (SMA) patients. We found that compound 53 improves delayed myogenesis in CDM1 myoblasts, while compounds 1 and 53 have neuroprotective properties in SMA-derived cells. These findings suggest that the allosteric modulators of GSK-3β may be used for future development of drugs for DM1, SMA, and other chronic diseases where GSK-3β inhibition exhibits therapeutic effects.
4-Hydroxy-2-quinolones. 149*. Synthesis, chemical transformations, and biological properties of β-N-acylhydrazides of 1-R-4-hydroxy-2-oxo-1,2- dihydro-quinoline-4-carboxylic acids
Ukrainets,Tkach,Yang, Liu Yang
experimental part, p. 1347 - 1354 (2009/05/27)
Two methods of preparation have been proposed and the synthesis has been effected of a large series of β-N-acylhydrazides of 1-R-4-hydroxy-2-oxo-1, 2-dihydroquinoline-3-carboxylic acids. The possibility of using various condensing agents for converting them into the corresponding 1,3,4-oxa-diazoloquinolines has been studied. Results are given of an investigation of the antitubercular activity of the synthesized compounds.
