(S)-N-[1-(3-morpholin-4-ylphenyl)ethyl]- 3-phenylacrylamide: an orally bioavailable KCNQ2 opener with significant activity in a cortical spreading depression model of migraine.
(S)-N-[1-(3-Morpholin-4-ylphenyl)ethyl]-3-phenylacrylamide (2) was synthesized as an orally bioavailable KCNQ2 potassium channel opener. In a rat model of migraine, 2 demonstrated significant oral activity in reducing the total number of cortical spreading depressions induced by potassium chloride.
Wu
Yong-Jin
YJ
Bristol-Myers Squibb Pharmaceutical Research Institute, 5 Research Parkway, Wallingford, Connecticut 06492, USA. yong-jin.wu@bms.com
Boissard
Christopher G
CG
Greco
Corinne
C
Gribkoff
Valentin K
VK
Harden
David G
DG
He
Huan
H
L'Heureux
Alexandre
A
Kang
Shing Hong
SH
Kinney
Gene G
GG
Knox
Ronald J
RJ
Natale
Joanne
J
Newton
Amy E
AE
Lehtinen-Oboma
Sanna
S
Sinz
Michael W
MW
Sivarao
Digavalli V
DV
Starrett
John E
JE
Sun
Li-Qiang
LQ
Tertyshnikova
Svetlana
S
Thompson
Mark W
MW
Weaver
David
D
Wong
Henry S
HS
Zhang
Lei
L
Dworetzky
Steven I
SI
D000178:Acrylamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002460:Cell Line; D002540:Cerebral Cortex / Q000187:drug effects* / Q000503:physiopathology; D004195:Disease Models, Animal; D004285:Dogs; D006801:Humans; D015640:Ion Channel Gating; D051658:KCNQ2 Potassium Channel; D008881:Migraine Disorders / Q000378:metabolism / Q000503:physiopathology*; D009025:Morpholines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D009865:Oocytes / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology; D024642:Potassium Channels, Voltage-Gated; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014982:Xenopus laevis
D000178:Acrylamides; D051658:KCNQ2 Potassium Channel; C496914:KCNQ2 protein, human; C496915:Kcnq2 protein, rat; D009025:Morpholines; C476437:N-(1-(3-morpholin-4-ylphenyl)ethyl)-3-phenylacrylamide; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated