The present study describes the discovery and characterization of a series of -(1-(1,1-dioxidotetrahydrothiophen-3-yl)-3-methyl-1-pyrazol-5-yl)acetamide ethers as G protein-gated inwardly-rectifying potassium (GIRK) channel activators. From our previous lead optimization efforts, we have identified a new ether-based scaffold and paired this with a novel sulfone-based head group to identify a potent and selective GIRK1/2 activator. In addition, we evaluated the compounds in tier 1 DMPK assays and have identified compounds that display nanomolar potency as GIRK1/2 activators with improved metabolic stability over the prototypical urea-based compounds.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8372201 | PMC |
| http://dx.doi.org/10.1039/d1md00129a | DOI Listing |
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