title: Potent antagonists of the Kv1.5 potassium channel: synthesis and evaluation of analogous N,N-diisopropyl-2-(pyridine-3-yl)acetamides.
abstract: This letter describes the discovery of a novel series of potent Kv1.5 ion channel antagonists based on a diisopropyl amide scaffold. Structure-activity relationships of functionalized analogs are discussed. Key compound 1-(3-(diisopropylcarbamoyl)-2-phenyl-3-(pyridin-3-yl)propyl)-3-(2-fluorobenzyl)urea (10) exhibits significant atrial-selective effects in an in vivo model.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, Merck and Co., Inc., PO Box 4, West Point, PA 19486, USA.
authors.forename: Kausik K
authors.initials: KK
authors.lastname: Nanda
authors.forename: M Brad
authors.initials: MB
authors.lastname: Nolt
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Cato
authors.forename: Stefanie A
authors.initials: SA
authors.lastname: Kane
authors.forename: Laszlo
authors.initials: L
authors.lastname: Kiss
authors.forename: Robert H
authors.initials: RH
authors.lastname: Spencer
authors.forename: Jixin
authors.initials: J
authors.lastname: Wang
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Lynch
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Regan
authors.forename: Gary L
authors.initials: GL
authors.lastname: Stump
authors.forename: Bing
authors.initials: B
authors.lastname: Li
authors.forename: Rebecca
authors.initials: R
authors.lastname: White
authors.forename: Suzie
authors.initials: S
authors.lastname: Yeh
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Bogusky
authors.forename: Mark T
authors.initials: MT
authors.lastname: Bilodeau
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Dinsmore
authors.forename: Craig W
authors.initials: CW
authors.lastname: Lindsley
authors.forename: George D
authors.initials: GD
authors.lastname: Hartman
authors.forename: Scott E
authors.initials: SE
authors.lastname: Wolkenberg
authors.forename: B Wesley
authors.initials: BW
authors.lastname: Trotter
mesh_terms: D000081:Acetamides / Q000138:chemical synthesis* / Q000494:pharmacology*; D000818:Animals; D004285:Dogs; D051666:Kv1.5 Potassium Channel / Q000037:antagonists & inhibitors*; D026902:Potassium Channel Blockers / Q000138:chemical synthesis* / Q000494:pharmacology*; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013997:Time Factors; D014508:Urea / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology
chemical_list: C515789:1-(3-(diisopropylcarbamoyl)-2-phenyl-3-(pyridin-3-yl)propyl)-3-(2-fluorobenzyl)urea; D000081:Acetamides; D051666:Kv1.5 Potassium Channel; D026902:Potassium Channel Blockers; D011725:Pyridines; D014508:Urea