title: Lactam sulfonamides as potent inhibitors of the Kv1.5 potassium ion channel.
abstract: A series of lactam sulfonamides has been discovered and optimized as inhibitors of the Kv1.5 potassium ion channel for treatment of atrial fibrillation. In vitro structure-activity relationships from lead structure C to optimized structure 3y are described. Compound 3y was evaluated in a rabbit PD-model and was found to selectively prolong the atrial effective refractory period at submicromolar concentrations.
authors: Respiratory, Inflammation & Autoimmunity iMed, AstraZeneca R&D Mölndal, SE-431 83 Mölndal, Sweden. Electronic address: Roine.I.Olsson@AstraZeneca.com.
authors: Roine I
authors: RI
authors: Olsson
authors: Cardiovascular & Metabolic Diseases iMed, AstraZeneca R&D Mölndal, SE-431 83 Mölndal, Sweden.
authors: Ingemar
authors: I
authors: Jacobson
authors: Cardiovascular & Metabolic Diseases iMed, AstraZeneca R&D Mölndal, SE-431 83 Mölndal, Sweden.
authors: Tommy
authors: T
authors: Iliefski
authors: Cardiovascular & Metabolic Diseases iMed, AstraZeneca R&D Mölndal, SE-431 83 Mölndal, Sweden.
authors: Jonas
authors: J
authors: Boström
authors: Cardiovascular & Metabolic Diseases iMed, AstraZeneca R&D Mölndal, SE-431 83 Mölndal, Sweden.
authors: Öjvind
authors: Ö
authors: Davidsson
authors: Cardiovascular & Metabolic Diseases iMed, AstraZeneca R&D Mölndal, SE-431 83 Mölndal, Sweden.
authors: Ola
authors: O
authors: Fjellström
authors: Cardiovascular & Metabolic Diseases iMed, AstraZeneca R&D Mölndal, SE-431 83 Mölndal, Sweden.
authors: Annika
authors: A
authors: Björe
authors: Cardiovascular & Metabolic Diseases iMed, AstraZeneca R&D Mölndal, SE-431 83 Mölndal, Sweden.
authors: Christina
authors: C
authors: Olsson
authors: Cardiovascular & Metabolic Diseases iMed, AstraZeneca R&D Mölndal, SE-431 83 Mölndal, Sweden.
authors: Johan
authors: J
authors: Sundell
authors: Cardiovascular & Metabolic Diseases iMed, AstraZeneca R&D Mölndal, SE-431 83 Mölndal, Sweden.
authors: Ulrik
authors: U
authors: Gran
authors: Cardiovascular & Metabolic Diseases iMed, AstraZeneca R&D Mölndal, SE-431 83 Mölndal, Sweden.
authors: Jonna
authors: J
authors: Gyll
authors: Respiratory, Inflammation & Autoimmunity iMed, AstraZeneca R&D Mölndal, SE-431 83 Mölndal, Sweden.
authors: Jesper
authors: J
authors: Malmberg
authors: Cardiovascular & Metabolic Diseases iMed, AstraZeneca R&D Mölndal, SE-431 83 Mölndal, Sweden.
authors: Olle
authors: O
authors: Hidestål
authors: Cardiovascular & Metabolic Diseases iMed, AstraZeneca R&D Mölndal, SE-431 83 Mölndal, Sweden.
authors: Hans
authors: H
authors: Emtenäs
authors: Respiratory, Inflammation & Autoimmunity iMed, AstraZeneca R&D Mölndal, SE-431 83 Mölndal, Sweden.
authors: Tor
authors: T
authors: Svensson
authors: Cardiovascular & Metabolic Diseases iMed, AstraZeneca R&D Mölndal, SE-431 83 Mölndal, Sweden.
authors: Zhong-Qing
authors: ZQ
authors: Yuan
authors: Cardiovascular & Metabolic Diseases iMed, AstraZeneca R&D Mölndal, SE-431 83 Mölndal, Sweden.
authors: Gert
authors: G
authors: Strandlund
authors: Respiratory, Inflammation & Autoimmunity iMed, AstraZeneca R&D Mölndal, SE-431 83 Mölndal, Sweden.
authors: Annika
authors: A
authors: Åstrand
authors: Cardiovascular & Metabolic Diseases iMed, AstraZeneca R&D Mölndal, SE-431 83 Mölndal, Sweden.
authors: Emma
authors: E
authors: Lindhardt
authors: Cardiovascular & Metabolic Diseases iMed, AstraZeneca R&D Mölndal, SE-431 83 Mölndal, Sweden.
authors: Gunilla
authors: G
authors: Linhardt
authors: Cardiovascular & Metabolic Diseases iMed, AstraZeneca R&D Mölndal, SE-431 83 Mölndal, Sweden.
authors: Elin
authors: E
authors: Forsström
authors: Cardiovascular & Metabolic Diseases iMed, AstraZeneca R&D Mölndal, SE-431 83 Mölndal, Sweden.
authors: Ågot
authors: Å
authors: Högberg
authors: Cardiovascular & Metabolic Diseases iMed, AstraZeneca R&D Mölndal, SE-431 83 Mölndal, Sweden.
authors: Frida
authors: F
authors: Persson
authors: Cardiovascular & Metabolic Diseases iMed, AstraZeneca R&D Mölndal, SE-431 83 Mölndal, Sweden.
authors: Birgit
authors: B
authors: Andersson
authors: Cardiovascular & Metabolic Diseases iMed, AstraZeneca R&D Mölndal, SE-431 83 Mölndal, Sweden.
authors: Anna
authors: A
authors: Rönnborg
authors: Cardiovascular & Metabolic Diseases iMed, AstraZeneca R&D Mölndal, SE-431 83 Mölndal, Sweden.
authors: Boel
authors: B
authors: Löfberg
mesh_terms: D000818:Animals; D004285:Dogs; D006207:Half-Life; D006801:Humans; D051666:Kv1.5 Potassium Channel / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007769:Lactams / Q000737:chemistry*; D026902:Potassium Channel Blockers / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D011760:Pyrrolidinones / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D011817:Rabbits; D051381:Rats; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics
chemical_list: D051666:Kv1.5 Potassium Channel; D007769:Lactams; D026902:Potassium Channel Blockers; D011760:Pyrrolidinones; D013449:Sulfonamides
keywords: Atrial fibrillation; IKur; Kv1.5; Lactams; Sulfonamides