title: Benzamide derivatives as blockers of Kv1.3 ion channel.
abstract: The voltage-gated potassium channel, Kv1.3, is present in human T-lymphocytes. Blockade of Kv1.3 results in T-cell depolarization, inhibition of T-cell activation, and attenuation of immune responses in vivo. A class of benzamide Kv1.3 channel inhibitors has been identified. The structure-activity relationship within this class of compounds in two functional assays, Rb_Kv and T-cell proliferation, is presented. In in vitro assays, trans isomers display moderate selectivity for binding to Kv1.3 over other Kv1.x channels present in human brain.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA. bao_jianming@merck.com
authors.forename: Shouwu
authors.initials: S
authors.lastname: Miao
authors.forename: Jianming
authors.initials: J
authors.lastname: Bao
authors.forename: Maria L
authors.initials: ML
authors.lastname: Garcia
authors.forename: Joung L
authors.initials: JL
authors.lastname: Goulet
authors.forename: Xingfang J
authors.initials: XJ
authors.lastname: Hong
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Kaczorowski
authors.forename: Frank
authors.initials: F
authors.lastname: Kayser
authors.forename: Gloria C
authors.initials: GC
authors.lastname: Koo
authors.forename: Andrew
authors.initials: A
authors.lastname: Kotliar
authors.forename: William A
authors.initials: WA
authors.lastname: Schmalhofer
authors.forename: Kashmira
authors.initials: K
authors.lastname: Shah
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Sinclair
authors.forename: Robert S
authors.initials: RS
authors.lastname: Slaughter
authors.forename: Marty S
authors.initials: MS
authors.lastname: Springer
authors.forename: Mary Jo
authors.initials: MJ
authors.lastname: Staruch
authors.forename: Nancy N
authors.initials: NN
authors.lastname: Tsou
authors.forename: Frederick
authors.initials: F
authors.lastname: Wong
authors.forename: William H
authors.initials: WH
authors.lastname: Parsons
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Rupprecht
mesh_terms: D001549:Benzamides / Q000138:chemical synthesis* / Q000494:pharmacology*; D001923:Brain Chemistry / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D051664:Kv1.3 Potassium Channel; D026902:Potassium Channel Blockers / Q000138:chemical synthesis* / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects*; D024642:Potassium Channels, Voltage-Gated; D012414:Rubidium Radioisotopes; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism
chemical_list: D001549:Benzamides; C496973:KCNA3 protein, human; D051664:Kv1.3 Potassium Channel; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D012414:Rubidium Radioisotopes