1448705-07-4Relevant academic research and scientific papers
Compound, composition, and method of activating GIRK potassium channel and use of same for treating conditions of interest
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Page/Page column 36; 37, (2015/07/07)
The present invention provides small molecule activators of GIRK potassium channels and methods for use thereof.
Discovery of 'molecular switches' within a GIRK activator scaffold that afford selective GIRK inhibitors
Wen, Wandong,Wu, Wenjun,Romaine, Ian M.,Kaufmann, Kristian,Du, Yu,Sulikowski, Gary A.,Weaver, C. David,Lindsley, Craig W.
, p. 4562 - 4566 (2013/08/23)
This letter describes a multi-dimensional SAR campaign based on a potent, efficacious and selective GIRK1/2 activator (～10-fold versus GIRK1/4 and inactive on nonGIRK 1-containing GIRKs, GIRK 2 or GIRK2/3). Further chemical optimization through an iterative parallel synthesis effort identified multiple 'molecular switches' that modulated the mode of pharmacology from activator to inhibitor, as well as engendering varying selectivity profiles for GIRK1/2 and GIRK1/4. Importantly, these compounds were all inactive on nonGIRK1 containing GIRK channels. However, SAR was challenging as subtle structural modifications had large effects on both mode of pharmacology and GIRK1/2 and GIRK1/4 channel selectivity.
