title: Novel cyclopentane dicarboxamide sodium channel blockers as a potential treatment for chronic pain.
abstract: A series of new voltage-gated sodium channel blockers were prepared based on the screening lead succinic diamide BPBTS. Replacement of the succinimide linker with the more rigid cyclic 1,2-trans-diamide linker was well tolerated. N-Methylation on the biphenylsulfonamide side of the amide moiety significantly reduced the clearance rate in rat pharmacokinetic studies.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA.
authors.forename: Pengchang P
authors.initials: PP
authors.lastname: Shao
authors.forename: Dong
authors.initials: D
authors.lastname: Ok
authors.forename: Michael H
authors.initials: MH
authors.lastname: Fisher
authors.forename: Maria L
authors.initials: ML
authors.lastname: Garcia
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Kaczorowski
authors.forename: Chunshi
authors.initials: C
authors.lastname: Li
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Lyons
authors.forename: William J
authors.initials: WJ
authors.lastname: Martin
authors.forename: Peter T
authors.initials: PT
authors.lastname: Meinke
authors.forename: Birgit T
authors.initials: BT
authors.lastname: Priest
authors.forename: McHardy M
authors.initials: MM
authors.lastname: Smith
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Wyvratt
authors.forename: Feng
authors.initials: F
authors.lastname: Ye
authors.forename: William H
authors.initials: WH
authors.lastname: Parsons
mesh_terms: D000284:Administration, Oral; D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D000700:Analgesics / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D001713:Biphenyl Compounds / Q000737:chemistry; D003517:Cyclopentanes / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use; D015640:Ion Channel Gating / Q000187:drug effects; D008745:Methylation; D008801:Mexiletine / Q000494:pharmacology; D010146:Pain / Q000188:drug therapy*; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D026941:Sodium Channel Blockers / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D013329:Structure-Activity Relationship; D013386:Succinates / Q000737:chemistry; D013449:Sulfonamides / Q000737:chemistry
chemical_list: D000577:Amides; D000700:Analgesics; D001713:Biphenyl Compounds; D003517:Cyclopentanes; D026941:Sodium Channel Blockers; D013386:Succinates; D013449:Sulfonamides; C502584:cyclopentane dicarboxamide; D008801:Mexiletine