Substituted biaryl oxazoles, imidazoles, and thiazoles as sodium channel blockers.
Voltage-gated sodium channels have been shown to play a critical role in neuropathic pain. With a goal to develop potent peripherally active sodium channel blockers, a series of low molecular weight biaryl substituted imidazoles, oxazoles, and thiazole carboxamides were identified with good in vitro and in vivo potency.
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
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; D006801:Humans; D007093:Imidazoles / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D008862:Microsomes, Liver / Q000378:metabolism; D062556:NAV1.7 Voltage-Gated Sodium Channel; D009437:Neuralgia / Q000188:drug therapy*; D010080:Oxazoles / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D026941:Sodium Channel Blockers / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D015222:Sodium Channels / Q000378:metabolism*; D013844:Thiazoles / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*
D007093:Imidazoles; D062556:NAV1.7 Voltage-Gated Sodium Channel; D010080:Oxazoles; C486866:SCN9A protein, human; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D013844:Thiazoles