GluN2B-NMDAR antagonist-2 (compound S-58) is a potent, selective and cross the blood-brain barrier NMDAR-GluN2B antagonist with an IC 50 value of 74.01, nM. GluN2B-NMDAR antagonist-2 shows mild cytotoxicity. GluN2B-NMDAR antagonist-2 decreases the cerebral infarction rates and neurologic deficit scores. GluN2B-NMDAR antagonist-2 has the potential for the research of stroke.