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ID: ALA2069205

Journal: Bioorg Med Chem Lett

Title: Identification of (R)-N-(4-(4-methoxyphenyl)thiazol-2-yl)-1-tosylpiperidine-2-carboxamide, ML277, as a novel, potent and selective K(v)7.1 (KCNQ1) potassium channel activator.

Authors: Mattmann ME, Yu H, Lin Z, Xu K, Huang X, Long S, Wu M, McManus OB, Engers DW, Le UM, Li M, Lindsley CW, Hopkins CR.

Abstract: A high-throughput screen utilizing a depolarization-triggered thallium influx through KCNQ1 channels was developed and used to screen the MLSMR collection of over 300,000 compounds. An iterative medicinal chemistry approach was initiated and from this effort, ML277 was identified as a potent activator of KCNQ1 channels (EC(50)=260 nM). ML277 was shown to be highly selective against other KCNQ channels (>100-fold selectivity versus KCNQ2 and KCNQ4) as well as against the distantly related hERG potassium channel.

CiteXplore: 22910039

DOI: 10.1016/j.bmcl.2012.07.060