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
  • 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.