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.
MeSH terms
-
Animals
-
Calcium Channels, L-Type / pharmacology
-
ERG1 Potassium Channel
-
Ether-A-Go-Go Potassium Channels / pharmacology
-
Evoked Potentials, Motor / drug effects*
-
Evoked Potentials, Motor / physiology
-
Heart Rate / drug effects*
-
Heart Rate / physiology
-
Humans
-
Kv1.5 Potassium Channel / antagonists & inhibitors*
-
Neuropsychological Tests
-
Potassium Channel Blockers / chemical synthesis*
-
Potassium Channel Blockers / pharmacology*
-
Semicarbazones / chemistry*
-
Semicarbazones / pharmacology*
-
Structure-Activity Relationship
-
Swine
Substances
-
Calcium Channels, L-Type
-
ERG1 Potassium Channel
-
Ether-A-Go-Go Potassium Channels
-
KCNH2 protein, human
-
Kv1.5 Potassium Channel
-
Potassium Channel Blockers
-
Semicarbazones