Novel Inhibitors of Potassium Ion Channels on Human T Lymphocytes

Article abstract of DOI:10.1021/jm00011a007

The in vitro biological characterization of a series of 4-(alkylamino)-1,4-dihydroquinolines is reported.These compounds are novel inhibitors of voltage-activated n-type potassium ion (K⁺) channels in human T lymphocytes.This series, identified from random screening, was found to inhibit <125I>charybdotoxin binding to n-type K⁺ channels with IC50 values ranging from 1E-6 to 1E-8 M.These analogs also inhibit whole cell n-type K⁺ currents with IC50 values from 1E-5 to 1E-7 M.The preparation of a series of new 4-(alkylamino)-1,4-dihydroquinolines is described.Structure-activity relationships are discussed.Naphthyl analog 7c, the best compound prepared, exhibited > 100-fold selectivity for inhibition of <125I>charybdotoxin binding to n-type K⁺ channels compared with inhibition of <3H>dofetilide binding to cardiac K⁺ channels.These compounds represent a potent and selective series of n-type K⁺ channel inhibitors that have the potential for further development as anti-inflammatory agents.