Discovery and synthesis of tetrahydroindolone-derived carbamates as Kv1.5 blockers

• Published in: Bioorganic & medicinal chemistry letters Vol. 16; no. 22; pp. 5855 - 5858
• Main Authors: Fluxe, Andrew, Wu, Shengde, Sheffer, James B., Janusz, John M., Murawsky, Michael, Fadayel, Gina M., Fang, Bin, Hare, Michelle, Djandjighian, Laurent
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 15-11-2006; Elsevier
• Subjects: Antiarythmic agents; Atrial antiarrhythmic; Biological and medical sciences; Calcium Channels, L-Type - pharmacology; Carbamate; Carbamates - chemistry; Carbamates - pharmacology; Cardiovascular system; ERG1 Potassium Channel; Ether-A-Go-Go Potassium Channels - pharmacology; Humans; In vitro efficacy; Indoles - chemistry; Indoles - pharmacology; Kv1.5 blocker; Kv1.5 Potassium Channel - antagonists & inhibitors; Medical sciences; Pharmacology. Drug treatments; Potassium Channel Blockers - chemical synthesis; Potassium Channel Blockers - pharmacology; Structure-Activity Relationship; Kv1.5 blocker; In vitro efficacy; Carbamate; Atrial antiarrhythmic; Heart; Atrium; Potassium channel antagonist; Nitrogen heterocycle; Selectivity; Antiarrhythmic agent; In vitro; Structure activity relation; Bicyclic compound; Indole derivatives; Chemical synthesis; Kvl.5 blocker
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2006.08.059

A novel class of tetrahydroindolone-derived carbamates has been discovered whose members are potent Kv1.5 blockers. The in vitro data show that compounds
6 and
29 are quite potent. They are also very selective over hERG (>450-fold) and L-type calcium channels (>450-fold).
A novel class of tetrahydroindolone-derived carbamates has been discovered whose members are potent Kv1.5 blockers. The in vitro data show that compounds
6 and
29 are quite potent. They are also very selective over hERG (>450-fold) and L-type calcium channels (>450-fold).