Statistical analysis on a series of glycine antagonists

Quantitative structure-activity relationships of two series of glycine antagonists, pyrido[2,3-b]pyrazines and pyrido[2,3-b]pyrazine N-oxides, was performed using PLS (Projection on Latent Variables) and traditional physico-chemical and topological descriptors. The effect of substitution on the heteroaromatic ring was investigated with the aim of further improving the affinity (expressed as pKi) of these derivatives towards the strychnine-insensitive glycine binding site associated with the NMDA receptor. A significant model was obtained for both series of compounds. Structure-activity implications are discussed.