Design and Synthesis of Novel Isoquinoline-3-nitriles as Orally Bioavailable Kv1.5 Antagonists for the Treatment of Atrial Fibrillation

Novel 3-cyanoisoquinoline Kv1.5 antagonists have been prepared and evaluated in in vitro and in vivo assays for inhibition of the Kv1.5 potassium channel and its associated cardiac potassium current, I Kur. Structural modifications of isoquinolinone lead 1 afforded compounds with excellent potency,...

Ausführliche Beschreibung

Gespeichert in:

Bibliographische Detailangaben
Veröffentlicht in:	Journal of medicinal chemistry 2006-11, Vol.49 (24), p.6954-6957
Hauptverfasser:	Trotter, B. Wesley, Nanda, Kausik K, Kett, Nathan R, Regan, Christopher P, Lynch, Joseph J, Stump, Gary L, Kiss, Laszlo, Wang, Jixin, Spencer, Robert H, Kane, Stefanie A, White, Rebecca B, Zhang, Rena, Anderson, Kenneth D, Liverton, Nigel J, McIntyre, Charles J, Beshore, Douglas C, Hartman, George D, Dinsmore, Christopher J
Format:	Artikel
Sprache:	eng
Schlagworte:	Administration, Oral Animals Anti-Arrhythmia Agents - chemical synthesis Anti-Arrhythmia Agents - chemistry Anti-Arrhythmia Agents - pharmacology Antiarythmic agents Atrial Fibrillation - drug therapy Biological and medical sciences Biological Availability Cardiovascular system Electrophysiology Heart - drug effects Heart - physiology Humans Isoquinolines - chemical synthesis Isoquinolines - chemistry Isoquinolines - pharmacology Kv1.5 Potassium Channel - antagonists & inhibitors Kv1.5 Potassium Channel - physiology Medical sciences Nitriles - chemical synthesis Nitriles - chemistry Nitriles - pharmacology Patch-Clamp Techniques Pharmacology. Drug treatments Rats Stereoisomerism Structure-Activity Relationship
Online-Zugang:	Volltext
Tags:	Tag hinzufügen Keine Tags, Fügen Sie den ersten Tag hinzu!

Beschreibung
Zusammenfassung:	Novel 3-cyanoisoquinoline Kv1.5 antagonists have been prepared and evaluated in in vitro and in vivo assays for inhibition of the Kv1.5 potassium channel and its associated cardiac potassium current, I Kur. Structural modifications of isoquinolinone lead 1 afforded compounds with excellent potency, selectivity, and oral bioavailability.
ISSN:	0022-2623 1520-4804
DOI:	10.1021/jm060927v