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

Abstract 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 ( 24 ) displayed sub-micromolar activity in both a thallium flux and whole-cell electrophysiology assay and did not displace apamin in a competitive binding study.