Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1369590 | Bioorganic & Medicinal Chemistry Letters | 2012 | 4 Pages |
Abstract
Further chemical optimization of the MLSCN/MLPCN probe ML077 (KCC2 IC50 = 537 nM) proved to be challenging as the effort was characterized by steep SAR. However, a multi-dimensional iterative parallel synthesis approach proved productive. Herein we report the discovery and SAR of an improved novel antagonist (VU0463271) of the neuronal-specific potassium-chloride cotransporter 2 (KCC2), with an IC50 of 61 nM and >100-fold selectivity versus the closely related Na-K-2Cl cotransporter 1 (NKCC1) and no activity in a larger panel of GPCRs, ion channels and transporters.
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Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Eric Delpire, Aleksandra Baranczak, Alex G. Waterson, Kwangho Kim, Nathan Kett, Ryan D. Morrison, J. Scott Daniels, C. David Weaver, Craig W. Lindsley,