Details

Autor(en) / Beteiligte

• Riva, Beatrice
• Griglio, Alessia
• Serafini, Marta
• Cordero-Sanchez, Celia
• Aprile, Silvio
• Di Paola, Rosanna
• Gugliandolo, Enrico
• Alansary, Dalia
• Biocotino, Isabella
• Lim, Dmitry
• Grosa, Giorgio
• Galli, Ubaldina
• Niemeyer, Barbara
• Sorba, Giovanni
• Canonico, Pier Luigi
• Cuzzocrea, Salvatore
• Genazzani, Armando A
• Pirali, Tracey

Titel

Pyrtriazoles, a Novel Class of Store-Operated Calcium Entry Modulators: Discovery, Biological Profiling, and in Vivo Proof-of-Concept Efficacy in Acute Pancreatitis

Ist Teil von

• Journal of medicinal chemistry, 2018-11, Vol.61 (21), p.9756-9783

Ort / Verlag

United States: American Chemical Society

Erscheinungsjahr

2018

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• In recent years, channels that mediate store-operated calcium entry (SOCE, i.e., the ability of cells to sense a decrease in endoplasmic reticulum luminal calcium and induce calcium entry across the plasma membrane) have been associated with a number of disorders, spanning from immune disorders to acute pancreatitis and have been suggested to be druggable targets. In the present contribution, we exploited the click chemistry approach to synthesize a class of SOCE modulators where the arylamide substructure that characterizes most inhibitors so far described is substituted by a 1,4-disubstituted 1,2,3-triazole ring. Within this series, inhibitors of SOCE were identified and the best compound proved effective in an animal model of acute pancreatitis, a disease characterized by a hyperactivation of SOCE. Strikingly, two enhancers of the process were discovered, affording invaluable research tools to further explore the (patho)­physiological role of capacitative calcium entry.