1001669-87-9Relevant academic research and scientific papers
Tau-Centric Multitarget Approach for Alzheimer's Disease: Development of First-in-Class Dual Glycogen Synthase Kinase 3β and Tau-Aggregation Inhibitors
Gandini, Annachiara,Bartolini, Manuela,Tedesco, Daniele,Martinez-Gonzalez, Loreto,Roca, Carlos,Campillo, Nuria E.,Zaldivar-Diez, Josefa,Perez, Concepción,Zuccheri, Giampaolo,Miti, Andrea,Feoli, Alessandra,Castellano, Sabrina,Petralla, Sabrina,Monti, Barbara,Rossi, Martina,Moda, Fabio,Legname, Giuseppe,Martinez, Ana,Bolognesi, Maria Laura
, p. 7640 - 7656 (2018)
Several findings propose the altered tau protein network as an important target for Alzheimer's disease (AD). Particularly, two points of pharmacological intervention can be envisaged: inhibition of phosphorylating tau kinase GSK-3β and tau aggregation process. On the basis of this consideration and on our interest in multitarget paradigms in AD, we report on the discovery of 2,4-thiazolidinedione derivatives endowed with such a profile. 28 and 30 displayed micromolar IC50 values toward GSK-3β, together with the capacity of inhibiting AcPHF6 aggregation of 60% and 80% at 10 μM, respectively. In addition, they showed PAMPA-BBB permeability, together with a suitable cellular safety profile. 30 also displayed inhibition of both K18 and full-length tau aggregations. Finally, both compounds were able to improve cell viability in an okadaic acid-induced neurodegeneration cell model. To the best of our knowledge, 28 and 30 are the first balanced, nontoxic, dual-acting compounds hitting tau cascade at two different hubs.
Compound capable of inhibiting activity of NEDD8 kinase as well as preparation method and pharmaceutical application of compound
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Paragraph 0072; 0073; 0074; 0146; 0147; 0149, (2016/10/10)
The invention belongs to the field of medicines and in particular relates to a compound with the structure of a formula I, a stereomer of the compound or pharmaceutically acceptable salts of the compound as well as a preparation method of the compound and application of the compound to preparation of anti-tumor medicines. A pharmacological experiment result shows that the compound can be used for inhibiting the activity of NEDD8 kinase and has the inhibition effect on proliferation of a plurality of types of tumor cells, so that the compound can be used as an NEDD8 kinase activity inhibitor for preparing the anti-tumor medicines. The formula I is shown in the description.
