Novel 2-Alkylamino-1,4-benzoxazine Derivatives as Potent Neuroprotective Agents: Structure−Activity Relationship Studies

2-Alkylamino-substituted-1,4-benzoxazine derivatives, a new class of potential neuroprotective agents, were synthesized and examined for their intrinsic cytotoxicity and their capacity to inhibit oxidative stress-mediated neuronal degeneration in vitro. Through structure-activity relationship studies, the 3,3-diphenyl-substituted-1,4-benzoxazine derivative 3l was identified as the optimal candidate, owing to its potent neuroprotective activity, without the manifestation of intrinsic cytotoxicity. Accordingly, 3l proved to be effective in an animal model of excitotoxic lesions in newborn mice.