Abstract: 5-(4-Hydroxyphenyl)-3H-1, 2-dithiole-3-thione(ADT-OH)is a slowly releasing H₂S donor with some neuroprotective effect. In order to study the structure-activity relationships, seventeen compounds( Y₁ - Y₁₇ )were synthesized by modification of ADT-OH at the aromatic ring position, and their structures were confirmed by ¹H NMR, ¹³C NMR and HR-MS. Among them, 6 compounds( Y₄, Y₁₃ - Y₁₇ )were novel compounds. Their effects had been evaluated on HT-22 hippocampal neuron cells damaged by glutamate with MTT method. The pharmacological results demonstrated that all the Y compounds had potent neuroprotection at most of the tested concentrations(1-100 μmol/L). Compounds Y₁ - Y₉ and Y₁₁ significantly improved the survival rates of the damaged cells at 1-100 μmol/L(P<0. 01). Specially, compounds Y₁, Y₄, Y₆ - Y₉, Y₁₁ are more potent than their parent compound ADT-OH at concentration of 1-10 μmol/L, which is worthy of further study.