Discovery of a novel class of isoxazoline voltage gated sodium channel blockers.
Analogs of the previously reported voltage gated sodium channel blocker CDA54 were prepared in which one of the amide functions was replaced with aromatic and non-aromatic heterocycles. Replacement of the amide with an aromatic heterocycle resulted in significant loss of sodium channel blocking activity, while non-aromatic heterocycle replacements were well tolerated.
Shao
Pengcheng P
PP
Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA. pengcheng_shao@merck.com
Ye
Feng
F
Weber
Ann E
AE
Li
Xiaohua
X
Lyons
Kathryn A
KA
Parsons
William H
WH
Garcia
Maria L
ML
Priest
Birgit T
BT
Smith
McHardy M
MM
Felix
John P
JP
Williams
Brande S
BS
Kaczorowski
Gregory J
GJ
McGowan
Erin
E
Abbadie
Catherine
C
Martin
William J
WJ
McMasters
Daniel R
DR
Gao
Ying-Duo
YD
D000818:Animals; D007555:Isoxazoles / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D008958:Models, Molecular; D015394:Molecular Structure; D010146:Pain / Q000188:drug therapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D026941:Sodium Channel Blockers / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D013127:Spinal Nerves / Q000187:drug effects; D013329:Structure-Activity Relationship
D007555:Isoxazoles; D026941:Sodium Channel Blockers