163562-46-7Relevant articles and documents
Novel Inhibitors of Potassium Ion Channels on Human T Lymphocytes
Michne, William F.,Guiles, Joseph W.,Treasurywala, Adi M.,Castonguay, Laurie A.,Weigelt, Carolyn A.,et al.
, p. 1877 - 1883 (1995)
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 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 charybdotoxin binding to n-type K+ channels compared with inhibition of 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.
