Discovery and synthesis of tetrahydroindolone derived semicarbazones as selective Kv1.5 blockers
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.
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
Dual photoredox/palladium-catalyzed C-H acylation of 2-arylpyridines with oxime esters
An unprecedented dual photoredox/palladium-catalyzed iminyl-radical-mediated C-C bond cleavage and directed ortho C-H acylation of 2-arylpyridines by using oxime esters is described. Oxime esters can serve as efficient acyl sources through formation of the corresponding acyl radicals by photoredox-catalyzed iminyl-radical-mediated C-C bond cleavage. This redox-neutral protocol features excellent regioselectivity, a broad substrate scope, and good functional-group tolerance with respect to both components, giving a broad range of aryl ketones with generally good yields.