A new series of 5-(2-aryloxy-4-nitrophenyl)-4H-1,2,4-triazoles and 5-(2-aryloxy-3-pyridyl)-4H-1,2,4-triazoles, possessing C-3 thio or alkylthio substituents, was synthesized and evaluated for their benzodiazepine receptor affinity and anti-seizure activity. These analogues revealed similar to significantly superior affinity to GABA_A/benzodiazepine receptor complex (IC₅₀ values of 0.04-4.1 nM), relative to diazepam as the reference drug (IC₅₀ value of 2.4 nM). To determine the onset of anti-seizure activity, the time-dependent effectiveness of i.p. administration of compounds on pentylenetetrazole induced seizure threshold was studied and a very good relationship was observed between the lipophilicity (cLog P) and onset of action of studied analogues (r² = 0.964). The minimum effective dose of the compounds, determined at the time the analogues showed their highest activity, was demonstrated to be 0.025-0.1 mg/kg, relative to diazepam (0.025 mg/kg).

新系列5-(2-芳氧基-4-硝基苯基)-4 H -1,2,4-三唑和5-(2-芳氧基-3-吡啶基)-4 H -1,2,4-三唑，合成了具有 C-3 硫代或烷硫基取代基的苯二氮卓受体亲和力和抗癫痫活性。相对于作为参考药物的地西泮（IC ₅₀值为2.4 nM），这些类似物显示出与GABA _A /苯二氮卓受体复合物（IC ₅₀值为0.04-4.1 nM）相似的显着优越的亲和力。确定抗癫痫活性的开始，ip的时间依赖性有效性研究了化合物给药对戊四唑诱发的癫痫阈值的影响，并且在亲脂性 (cLog P) 和所研究类似物的作用开始之间观察到非常好的关系 (r ² = 0.964)。在类似物显示其最高活性时确定的化合物的最小有效剂量相对于地西泮 (0.025 mg/kg) 为 0.025-0.1 mg/kg。