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The activity of the new derivatives against oxidative stress induced neuronal damage, was evaluated using glutamate-challenged hippocampal HT22 cells. Compound 3 in which a 3,4-dimethoxyphenyl moiety, is directly attached to the 1,2,4-oxadiazole ring was the most active among the 2-substituted chroman analogues, with EC(50) = 254 +/- 65 nM. Concerning the 5-subtituted chroman analogues, isoxazole derivative 29 exhibited the strongest activity (EC(50) = 245 +/- 38 nM). 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