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

An exploratory SAR study on a series of non-apamin-displacing 4-(aminomethylaryl)pyrazolopyrimidine K Ca channel blockers is described, and their selectivity against K Ca channel subtypes is reported. The aminomethylthiophene derivative 24, was the most potent analog identified in the series. An exp...

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Published inBioorganic & medicinal chemistry letters Vol. 18; no. 20; pp. 5694 - 5697
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
LanguageEnglish
Published Elsevier Ltd 15.10.2008
Subjects
Apamin
Non-apamin displacing
Pyrrazolopyrimidine
Small conductance potassium channel
Non-apamin displacing
Pyrrazolopyrimidine
Apamin
Small conductance potassium channel
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Summary:An exploratory SAR study on a series of non-apamin-displacing 4-(aminomethylaryl)pyrazolopyrimidine K Ca channel blockers is described, and their selectivity against K Ca channel subtypes is reported. The aminomethylthiophene derivative 24, was the most potent analog identified in the series. 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.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2008.08.026