2026-04-20T09:12:38Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/165682024-09-27T08:34:16Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Milani, Gualtiero author Budriesi, Roberta author Tavazzani, Elisa author Cavalluzzi, Maria Maddalena author Mattioli, Laura Beatrice author Miniero, Daniela Valeria author Delre, Pietro author Belviso, Benny Danilo author Denegri, Marco author Cuocci, Corrado author Rotondo, Natalie Paola author De Palma, Annalisa author Gualdani, Roberta author Caliandro, Rocco author Mangiatordi, Giuseppe Felice author Kumawat, Amit author Camilloni, Carlo author Priori, Silvia G. author Lentini, Giovanni author 2023-10 Long QT syndrome (LQTS) is a disorder of cardiac electrophysiology resulting in life-threatening arrhythmias; nowadays, only a few drugs are available for the management of LQTS. Focusing our attention on LQT2, one of the most common subtypes of LQTS caused by mutations in the human ether-à-go-go-related gene (hERG), in the present work, the stereoselectivity of the recently discovered mexiletine-derived urea 8 was investigated on the hERG potassium channel. According to preliminary in silico predictions, in vitro studies revealed a stereoselective behavior, with the meso form showing the greatest hERG opening activity. In addition, functional studies on guinea pig isolated left atria, aorta, and ileum demonstrated that 8 does not present any cardiac or intestinal liability in our ex vivo studies. Due to its overall profile, (R,S)-8 paves the way for the design and development of a new series of compounds potentially useful in the treatment of both congenital and drug-induced forms of LQTS. Arch Pharm (Weinheim). 2023 Oct;356(10):e2300116. http://hdl.handle.net/20.500.12105/16568 37460390 10.1002/ardp.202300116 1521-4184 Archiv der Pharmazie hERG stereoselective modulation by mexiletine-derived ureas: Molecular docking study, synthesis, and biological evaluation.