Description:
<jats:title>Abstract</jats:title><jats:p>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 <jats:italic>α</jats:italic>1 and <jats:italic>α</jats:italic>1<jats:italic>β</jats:italic> glycine receptors were evaluated. Isostrychnine has shown the best pharmacological profile exhibiting an <jats:italic>IC</jats:italic><jats:sub>50</jats:sub> value of 1.6 μ<jats:sc>M</jats:sc> at <jats:italic>α</jats:italic>1 glycine receptors and 3.7‐fold preference towards the <jats:italic>α</jats:italic>1 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</jats:p>