Preliminary SAR studies on non-apamin-displacing 4-(aminomethylaryl)pyrrazolopyrimidine K(Ca) channel blockers

• Published in: Bioorganic & medicinal chemistry letters Vol. 18; no. 20; p. 5694
• Main Authors: Gentles, Robert G, Hu, Shuanghua, Huang, Yazhong, Grant-Young, Katherine, Poss, Michael A, Andres, Charles, Fiedler, Tracey, Knox, Ronald, Lodge, Nicholas, Weaver, C David, Harden, David G
• Format: Journal Article
• Language: English
• Published: England 15.10.2008
• Subjects: Apamin - chemistry; Binding, Competitive; Cell Line; Electrophysiology; Humans; Inhibitory Concentration 50; Models, Chemical; Potassium Channel Blockers - chemistry; Potassium Channels, Calcium-Activated - metabolism; Protein Isoforms; Pyrazoles - chemical synthesis; Pyrazoles - pharmacology; Pyrimidines - chemical synthesis; Pyrimidines - chemistry; Pyrimidines - pharmacology; Structure-Activity Relationship; Thallium - chemistry

An exploratory SAR study on a series of potent, non-apamin-displacing 4-(aminomethylaryl)pyrazolopyrimidine K(Ca) channel blockers is described and their selectivity against K(Ca) channel subtypes is reported. The most potent analog, 5-chloro-N-(thiophen-2-ylmethyl)pyrazolo[1,5-a]pyrimidin-7-amine (...