Pyrimidinederivativeshavebeenreportedasneuroprotectiveagentsusefulforthetreatmentofvariousneurodegenerativedisorders.Inthepresentstudy,severalpyrimidineanalogueshavebeenevaluatedasneuroprotectiveagentsinMorriswatermazemodel.Itwasobservedthatpyrimidinederivatives8–17considerablyimprovelearning,memory,andmovementdeficitsinanimalmodels.Biochemicalestimationsofbrainserumoftreatedanimalsrevealedsuppressionofoxidativeandnitrosativestress,acetylcholinesteraseactivity,andotherparameterswhichleadstoneurodegenerationofbrain.Ofallthepyrimidinederivatives,thiomorpholinederivative8andpiperazineethanolderivative17werefoundtobethemostactiveneuroprotectiveagentsandproducedeffectscomparabletostandarddrugrivastigmineintermsofbehavioral,biochemical,andmolecularaspects.