title: Novel 5-cyclopropyl-1,4-benzodiazepin-2-ones as potent and selective I(Ks)-blocking class III antiarrhythmic agents.
abstract: Novel 5-cyclopropyl-1,4-benzodiazepin-2-ones having various N-l substituents were identified as potent and selective blockers of the slowly activating cardiac delayed rectifier potassium current (I(Ks)). Compound 11 is the most potent I(Ks) channel blocker reported to date.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA.
authors.forename: John W
authors.initials: JW
authors.lastname: Butcher
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Liverton
authors.forename: David A
authors.initials: DA
authors.lastname: Claremon
authors.forename: Roger M
authors.initials: RM
authors.lastname: Freidinger
authors.forename: Nancy K
authors.initials: NK
authors.lastname: Jurkiewicz
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Lynch
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Salata
authors.forename: Jixin
authors.initials: J
authors.lastname: Wang
authors.forename: Christine M
authors.initials: CM
authors.lastname: Dieckhaus
authors.forename: Donald E
authors.initials: DE
authors.lastname: Slaughter
authors.forename: Kamlesh
authors.initials: K
authors.lastname: Vyas
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D001569:Benzodiazepines / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D051668:Delayed Rectifier Potassium Channels; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008862:Microsomes, Liver / Q000378:metabolism; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects*; D024642:Potassium Channels, Voltage-Gated; D012032:Refractory Period, Electrophysiological / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D000889:Anti-Arrhythmia Agents; D051668:Delayed Rectifier Potassium Channels; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D001569:Benzodiazepines