Discovery and synthesis of tetrahydroindolone-derived carbamates as Kv1.5 blockers.
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).
Fluxe
Andrew
A
Procter and Gamble Pharmaceuticals, Mason Business Center, 8700 Mason-Montgomery Road, Mason, OH 45040, USA. fluxe_cj@yahoo.com
Wu
Shengde
S
Sheffer
James B
JB
Janusz
John M
JM
Murawsky
Michael
M
Fadayel
Gina M
GM
Fang
Bin
B
Hare
Michelle
M
Djandjighian
Laurent
L
D020746:Calcium Channels, L-Type / Q000494:pharmacology; D002219:Carbamates / Q000737:chemistry* / Q000494:pharmacology*; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels / Q000494:pharmacology; D006801:Humans; D007211:Indoles / Q000737:chemistry* / Q000494:pharmacology*; D051666:Kv1.5 Potassium Channel / Q000037:antagonists & inhibitors*; D026902:Potassium Channel Blockers / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D020746:Calcium Channels, L-Type; D002219:Carbamates; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D007211:Indoles; C000606913:KCNH2 protein, human; D051666:Kv1.5 Potassium Channel; D026902:Potassium Channel Blockers