Pseudosaccharin amines as potent and selective KV1.5 blockers

Abstract 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.