- Ramos-Hunter SJ, Engers DW, Kaufmann K, Du Y, Lindsley CW, Weaver CD, Sulikowski GA. Discovery and SAR of a novel series of GIRK1/2 and GIRK1/4 activators. Bioorganic & medicinal chemistry letters. 2013 Sep 9;23(18). 5195-8. PMID: 23916258 [PubMed].
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.
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