Statistical analysis on a series of glycine antagonists

Abstract

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 p K i) 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.