130058-54-7Relevant articles and documents
Palladium-Catalyzed Cyclization Reaction of o-Iodoanilines, CO2, and CO: Access to Isatoic Anhydrides
Zhang, Wen-Zhen,Zhang, Ning,Sun, Yu-Qian,Ding, Yu-Wei,Lu, Xiao-Bing
, p. 8072 - 8076 (2017/12/08)
Isatoic anhydrides, a class of valuable synthetic intermediates and RNA structure probing reagents, are usually prepared with highly toxic phosgene or stoichiometric oxidants. Herein we report a highly selective palladium-catalyzed cyclization reaction for the efficient synthesis of isatoic anhydrides from readily available o-iodoanilines, CO2, and CO. The reaction proceeds under mild conditions and is redox-neutral. Both CO2 and CO are indispensable C1 building blocks for this catalytic reaction.
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.
Design, synthesis and biological characterization of a new class of osteogenic (1H)-quinolone derivatives
Manetti, Fabrizio,Petricci, Elena,Gabrielli, Annalisa,Mann, Andrè,Faure, Hélène,Gorojankina, Tatiana,Brasseur, Laurent,Hoch, Lucile,Ruat, Martial,Taddei, Maurizio
, p. 747 - 757 (2016/07/21)
Smoothened (Smo) is the signal transducer of the Hedgehog (Hh) pathway and its stimulation is considered a potential powerful tool in regenerative medicine to treat severe tissue injuries. Starting from GSA-10, a recently reported Hh activator acting on Smo, we have designed and synthesized a new class of quinolone-based compounds. Modification and decoration of three different portions of the original scaffold led to compounds able to induce differentiation of multipotent mesenchymal cells into osteoblasts. The submicromolar activity of several of these new quinolones (0.4–0.9?μM) is comparable to or better than that of SAG and purmorphamine, two reference Smo agonists. Structure-activity relationships allow identification of several molecular determinants important for the activity of these compounds.
