Structure–activity relationship study of novel NR2B-selective antagonists with arylamides to avoid reactive metabolites formation

A novel potent NMDA-NR2B selective antagonist (5b) without the reactive metabolites formation issue was identified. Through this study, a close correlation between reactive metabolites formation and calculated HOMO energies of parent compounds was found.

Replacement of the phenol moiety with pyrazole led to a novel potent NMDA-NR2B selective antagonist (5b) with an improved metabolic profile. Through this study, a close correlation between reactive metabolites formation and calculated HOMO energies of parent compounds was found.Figure optionsDownload as PowerPoint slide