2. Academic Validation
  3. Discovery and SAR of a novel series of GIRK1/2 and GIRK1/4 activators

Discovery and SAR of a novel series of GIRK1/2 and GIRK1/4 activators

  • Bioorg Med Chem Lett. 2013 Sep 15;23(18):5195-8. doi: 10.1016/j.bmcl.2013.07.002.
Susan J Ramos-Hunter 1,  Darren W Engers,  Kristian Kaufmann,  Yu Du,  Craig W Lindsley,  C David Weaver,  Gary A Sulikowski
Affiliations

Affiliation

  • 1 Department of Chemistry, Vanderbilt University, Nashville, TN 37232, USA.
PMID: 23916258 DOI: 10.1016/j.bmcl.2013.07.002
Abstract

This Letter describes a novel series of GIRK activators identified through an HTS campaign. The HTS lead was a potent and efficacious dual GIRK1/2 and GIRK1/4 activator. Further chemical optimization through both iterative parallel synthesis and fragment library efforts identified dual GIRK1/2 and GIRK1/4 activators as well as the first examples of selective GIRK1/4 activators. Importantly, these compounds were inactive on GIRK2 and Other non-GIRK1 containing GIRK channels, and SAR proved shallow.

Keywords

Activators; GIRK; K(ir)3.x; Thallium flux.

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