Imidazopyridines: a novel class of hNav1.7 channel blockers.
A series of imidazopyridines were evaluated as potential sodium channel blockers for the treatment of neuropathic pain. Several members were identified with good hNa(v)1.7 potency and excellent rat pharmacokinetic profiles. Compound 4 had good efficacy (52% and 41% reversal of allodynia at 2 and 4h post-dose, respectively) in the Chung rat spinal nerve ligation (SNL) model of neuropathic pain when dosed orally at 10mg/kg.
London
Clare
C
Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA. clare_london@merck.com
Hoyt
Scott B
SB
Parsons
William H
WH
Williams
Brande S
BS
Warren
Vivien A
VA
Tschirret-Guth
Richard
R
Smith
McHardy M
MM
Priest
Birgit T
BT
McGowan
Erin
E
Martin
William J
WJ
Lyons
Kathryn A
KA
Li
Xiaohua
X
Karanam
Bindhu V
BV
Jochnowitz
Nina
N
Garcia
Maria L
ML
Felix
John P
JP
Dean
Brian
B
Abbadie
Catherine
C
Kaczorowski
Gregory J
GJ
Duffy
Joseph L
JL
D000700:Analgesics / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D007249:Inflammation / Q000188:drug therapy; D015394:Molecular Structure; D062556:NAV1.7 Voltage-Gated Sodium Channel; D010146:Pain / Q000188:drug therapy; D011725:Pyridines / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D026941:Sodium Channel Blockers / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D015222:Sodium Channels / Q000378:metabolism*; D013329:Structure-Activity Relationship
D000700:Analgesics; D062556:NAV1.7 Voltage-Gated Sodium Channel; D011725:Pyridines; C486866:SCN9A protein, human; D026941:Sodium Channel Blockers; D015222:Sodium Channels