Discovery and synthesis of tetrahydroindolone derived semicarbazones as selective Kv1. 5 blockers

…, B Blass, K Cobum, R Hedges, M Murawsky…

Index: Wu, Shengde; Fluxe, Andrew; Janusz, John M.; Sheffer, James B.; Browning, Greg; Blass, Benjamin; Cobum, Keith; Hedges, Richard; Murawsky, Michael; Fang, Bin; Fadayel, Gina M.; Hare, Michelle; Djandjighian, Laurent Bioorganic and Medicinal Chemistry Letters, 2006 , vol. 16, # 22 p. 5859 - 5863

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Citation Number: 29

Abstract

A novel class of tetrahydroindolone-derived semicarbazones has been discovered as potent Kv1. 5 blockers. In in vitro studies, several compounds exhibited very good potency for blockade of Kv1. 5. Compound 8i showed good selectivity for blockade of Kv1. 5 vs hERG and L-type calcium channels. In an anesthetized pig model, compounds 8i and 10c increased atrial ERP about 28%, 18%, respectively, in the right atrium without affecting ...