Pseudosaccharin Amines As Potent And Selective K(V)1.5 Blockers

Phenethyl aminoheterocycles like compound 1 were known to be potent I-Kur blockers although they lacked potency in vivo. Modification of the heterocycle led to the design and synthesis of pseudosaccharin amines. Compounds such as 14, 17d and 21c were found to be potent K(V)1.5 blockers and selective over other cardiac ion channels. These compounds had potent pharmacodynamic activity, however, they also showed off-target activities such as hemodynamic effects. (C) 2015 Elsevier Ltd. All rights reserved.