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ID: ALA1137272

Journal: Bioorg Med Chem Lett

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

Authors: Wu S, Fluxe A, Janusz JM, Sheffer JB, Browning G, Blass B, Cobum K, Hedges R, Murawsky M, Fang B, Fadayel GM, Hare M, Djandjighian L.

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 ventricular ERP.

CiteXplore: 16942874

DOI: 10.1016/j.bmcl.2006.08.057