Discovery of (S,E)-3-(2-fluorophenyl)-N-(1-(3-(pyridin-3-yloxy)phenyl)ethyl)-acrylamide as a potent and efficacious KCNQ2 (Kv7.2) opener for the treatment of neuropathic pain.
Acrylamide (S)-6, a potent and efficacious KCNQ2 (Kv7.2) opener, demonstrated significant activity in two models of neuropathic pain and in the formalin test, suggesting that KCNQ2 openers may be useful in the treatment of neuropathic pain including diabetic neuropathy.
Research and Development, Bristol-Myers Squibb Company, 5 Research Parkway, Wallingford, CT 06492, USA. Electronic address: yong-jin.wu@bms.com.
Yong-Jin
YJ
Wu
Charles M
CM
Conway
Li-Qiang
LQ
Sun
Frederic
F
Machet
Jie
J
Chen
Ping
P
Chen
Huan
H
He
Clotilde
C
Bourin
Vincenzo
V
Calandra
Joseph L
JL
Polino
Carl D
CD
Davis
Karen
K
Heman
Valentin K
VK
Gribkoff
Christopher G
CG
Boissard
Ronald J
RJ
Knox
Mark W
MW
Thompson
William
W
Fitzpatrick
David
D
Weaver
David G
DG
Harden
Joanne
J
Natale
Steven I
SI
Dworetzky
John E
JE
Starrett
D000178:Acrylamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D051658:KCNQ2 Potassium Channel / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D009437:Neuralgia / Q000188:drug therapy*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley
D000178:Acrylamides; D051658:KCNQ2 Potassium Channel
Acrylamide; Diabetic neuropathy; KCNQ2; Kv7.2; Neuropathic pain