Substituted biaryl pyrazoles as sodium channel blockers.
Voltage-gated sodium channels have been shown to play a critical role in neuropathic pain. A series of low molecular weight biaryl substituted pyrazole carboxamides were identified with good in-vitro potency and in-vivo efficacy. Compound 26, a Nav1.7 blocker has excellent efficacy in the Chung model of neuropathic pain.
Tyagarajan
Sriram
S
Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA. sriram_tyagarajan@merck.com
Chakravarty
Prasun K
PK
Zhou
Bishan
B
Taylor
Brett
B
Fisher
Michael H
MH
Wyvratt
Mathew J
MJ
Lyons
Kathy
K
Klatt
Tracy
T
Li
Xiaohua
X
Kumar
Sanjeev
S
Williams
Brande
B
Felix
John
J
Priest
Birgit T
BT
Brochu
Richard M
RM
Warren
Vivien
V
Smith
McHardy
M
Garcia
Maria
M
Kaczorowski
Gregory J
GJ
Martin
William J
WJ
Abbadie
Catherine
C
McGowan
Erin
E
Jochnowitz
Nina
N
Parsons
William H
WH
D000818:Animals; D004285:Dogs; D000882:Haplorhini; D006801:Humans; D008862:Microsomes, Liver / Q000378:metabolism; D062556:NAV1.7 Voltage-Gated Sodium Channel; D009437:Neuralgia / Q000188:drug therapy*; D011720:Pyrazoles / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D026941:Sodium Channel Blockers / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D015222:Sodium Channels / Q000378:metabolism*; D013329:Structure-Activity Relationship
D062556:NAV1.7 Voltage-Gated Sodium Channel; D011720:Pyrazoles; C486866:SCN9A protein, human; D026941:Sodium Channel Blockers; D015222:Sodium Channels