Structure-activity relationships of strychnine analogs at glycine receptors

Abstract

Nine strychnine derivatives including neostrychnine, strychnidine, isostrychnine, 21,22-dihydro-21-hydroxy-22-oxo-strychnine, and several hydrogenated analogs were synthesized, and their antagonistic activities at human α1 and α1β glycine receptors were evaluated. Isostrychnine has shown the best pharmacological profile exhibiting an IC 50 value of 1.6μM at α1 glycine receptors and 3.7-fold preference towards the α1 subtype. SAR Analysis indicates that the lactam moiety and the C(21) C(22) bond in strychnine are essential structural features for its high antagonistic potency at glycine receptors Copyright © 2014 Verlag Helvetica Chimica Acta AG, Zürich.