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ID: ALA2417534

Journal: Bioorg Med Chem Lett

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

Authors: Ramos-Hunter SJ, Engers DW, Kaufmann K, Du Y, Lindsley CW, Weaver CD, Sulikowski GA.

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.

CiteXplore: 23916258

DOI: 10.1016/j.bmcl.2013.07.002