Neuroprotective Effects of N-Alkyl-1,2,4-oxadiazolidine-3,5-diones and Their Corresponding Synthetic Intermediates N-Alkylhydroxylamines and N-1-Alkyl-3-carbonyl-1-hydroxyureas against in vitro Cerebral Ischemia

Herein we report the synthesis and neuroprotective effects of new N-alkyl-1,2,4-oxadiazolidine-3,5-diones and their corresponding synthetic intermediates, N-alkylhydroxylamines and N-1-alkyl-3-carbonyl-l-hydroxyureas, in an in vitro model of ischemia. We found five analogues that protect HT22 cells from death in the concentration range of 1-5 mu M. Because members of the MAP kinase family are known to be key players in nerve cell survival and death, we characterized the role of these kinases in the neuroprotective mechanisms of the newly synthesized analogues. The results indicate that these compounds provide neuroprotection through distinct mechanisms of action.