Development of GoSlo-SR-5-69, a potent activator of large conductance Ca2+-activated K+ (BK) channels

摘要: We have designed, synthesised and characterised the effects of a number novel anthraquinone derivatives assessed their on large conductance, Ca2+ activated K+ (BK) channels recorded from rabbit bladder smooth muscle cells using excised, inside/out configuration patch clamp technique. These compounds are members GoSlo-SR family compounds, which potently open BK shift voltage required for half maximal activation (V1/2) negatively. The efficacy anilinoanthraquinone was enhanced when size ring D increased, since cyclopentane cyclohexane shifted V1/2, by −24 ± 6 mV −54 8 mV, respectively, whereas cycloheptane cyclooctane V1/2 −61 −106 mV. To examine if combination hydrophobicity steric bulking this region further ability to channels, we naphthalene tetrahydro-naphthalene derivatives. tetrahydro-2-naphthalene derivative GoSlo-SR-5-69 most potent efficacious series it able greater than −100 applied at concentration 1 μM had an EC50 251 nM, making one channel openers date.