title: Discovery of isoxazole voltage gated sodium channel blockers for treatment of chronic pain.
abstract: A series of novel isoxazole voltage gated sodium channel blockers have been synthesized and evaluated. Substitutions on the benzylic position of benzamide were investigated to determine their effect on Na(v)1.7 inhibitory potency. The spirocyclobutyl substitution had the most significant enhancement on Na(v)1.7 inhibitory activity.
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; D002460:Cell Line; D002908:Chronic Disease; D006801:Humans; D007555:Isoxazoles / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D010146:Pain / Q000188:drug therapy* / Q000276:immunology; D051381:Rats; D026941:Sodium Channel Blockers / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D015222:Sodium Channels / Q000378:metabolism*; D013127:Spinal Nerves / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D007555:Isoxazoles; D026941:Sodium Channel Blockers; D015222:Sodium Channels