Author/Authors :
Shengde Wu، نويسنده , , Andrew Fluxe، نويسنده , , John M. Janusz، نويسنده , , James B. Sheffer، نويسنده , , R. Greg Browning، نويسنده , , Benjamin Blass، نويسنده , , Keith Cobum، نويسنده , , Richard Hedges، نويسنده , , Michael Murawsky، نويسنده , , Bin Fang، نويسنده , , Gina M. Fadayel، نويسنده , , Michelle Hare، نويسنده , , Laurent Djandjighian، نويسنده ,
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.
Keywords :
Semicarbazone , Kv1.5 Inhibitor , Atrial antiarrhythmic , In-vivo efficacy
