title: Discovery of a novel class of isoxazoline voltage gated sodium channel blockers.
abstract: 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.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA. pengcheng_shao@merck.com
authors.forename: Pengcheng P
authors.initials: PP
authors.lastname: Shao
authors.forename: Feng
authors.initials: F
authors.lastname: Ye
authors.forename: Ann E
authors.initials: AE
authors.lastname: Weber
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Li
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Lyons
authors.forename: William H
authors.initials: WH
authors.lastname: Parsons
authors.forename: Maria L
authors.initials: ML
authors.lastname: Garcia
authors.forename: Birgit T
authors.initials: BT
authors.lastname: Priest
authors.forename: McHardy M
authors.initials: MM
authors.lastname: Smith
authors.forename: John P
authors.initials: JP
authors.lastname: Felix
authors.forename: Brande S
authors.initials: BS
authors.lastname: Williams
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Kaczorowski
authors.forename: Erin
authors.initials: E
authors.lastname: McGowan
authors.forename: Catherine
authors.initials: C
authors.lastname: Abbadie
authors.forename: William J
authors.initials: WJ
authors.lastname: Martin
authors.forename: Daniel R
authors.initials: DR
authors.lastname: McMasters
authors.forename: Ying-Duo
authors.initials: YD
authors.lastname: Gao
mesh_terms: 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
chemical_list: D007555:Isoxazoles; D026941:Sodium Channel Blockers