2. Academic Validation
  3. Preliminary SAR studies on non-apamin-displacing 4-(aminomethylaryl)pyrrazolopyrimidine K(Ca) channel blockers

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

  • Bioorg Med Chem Lett. 2008 Oct 15;18(20):5694-7. doi: 10.1016/j.bmcl.2008.08.026.
Robert G Gentles 1,  Shuanghua Hu,  Yazhong Huang,  Katherine Grant-Young,  Michael A Poss,  Charles Andres,  Tracey Fiedler,  Ronald Knox,  Nicholas Lodge,  C David Weaver,  David G Harden
Affiliations

Affiliation

  • 1 Research and Development, Bristol Myers Squibb Co., 5 Research Parkway, Wallingford, CT, USA. [email protected]
PMID: 18824351 DOI: 10.1016/j.bmcl.2008.08.026
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.

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