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Published on: June 23, 2019
Optimization of Pyrazole-Based Activators of Kv3.1
Paul K Spearing1, Vaishali Satpute Janke2, Ian M Romaine3
1Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee 37232, United States.
Abstract:
Potentiators of the Kv3.1 voltage-gated potassium channel may have utility as therapies for certain CNS disorders. A SAR survey around a previously reported Kv3.1 activator scaffold led to the identification of compounds with superior potency and higher activation levels than reported molecules. We further demonstrated that these compounds show relevant activity in a patch-clamp electrophysiology assay. Together, the defined tractability in the chemotype and the promising biological activity indicate that these compounds may be leads for continued optimization toward therapies for neurological disorders.
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