Discovery and in vitro/in vivo studies of tetrazole derivatives as Kv1.5 blockers.
A novel class of tetrazole-derived Kv1.5 blockers is disclosed. In in vitro studies, several compounds had IC(50)s ranging from 180 to 550 nM. In vivo studies indicated that compounds 2f and 2j increased right atrial ERP about 40% without affecting ventricular ERP.
Wu
Shengde
S
Procter & Gamble Pharmaceuticals, Health Care Research Center, 8700 Mason-Montgomery Road, Mason, OH 45040, USA. wu.s.3@pg.com
Fluxe
Andrew
A
Sheffer
Jim
J
Janusz
John M
JM
Blass
Benjamin E
BE
White
Ron
R
Jackson
Chris
C
Hedges
Richard
R
Murawsky
Michael
M
Fang
Bin
B
Fadayel
Gina M
GM
Hare
Michelle
M
Djandjighian
Laurent
L
D000818:Animals; D006339:Heart Rate / Q000187:drug effects; D007700:Kinetics; D051666:Kv1.5 Potassium Channel / Q000037:antagonists & inhibitors*; D008958:Models, Molecular; D013329:Structure-Activity Relationship; D013552:Swine; D013556:Swine, Miniature; D013777:Tetrazoles / Q000737:chemistry / Q000494:pharmacology*; D013844:Thiazoles / Q000737:chemistry / Q000494:pharmacology*
D051666:Kv1.5 Potassium Channel; D013777:Tetrazoles; D013844:Thiazoles