Chaudhary S K, Chaudhary M, Chaudhari A, Parmar S S
J Pharm Sci. 1978 Nov;67(11):1507-9. doi: 10.1002/jps.2600671104.
Eight 5-(3,4-methylenedioxyphenyl)-3-arylaminomethyl-1,3,4-oxadiazole-2-thiones were synthesized, characterized by their sharp melting points, elemental analyses, and IR spectra, and evaluated for anticonvulsant activity. All substituted oxadiazole-2-thiones possessed anticonvulsant activity, which was reflected by their ability to provide 10--70% protection against pentylenetetrazol-induced convulsions in mice at 100 mg/kg ip. These compounds inhibited in vitro nicotinamide adenine dinucleotide (NAD)-dependent oxidation of pyruvate, alpha-ketoglutarate, and NADH by rat brain homogenates as well as NAD-independent oxidation of succinate by rat brain homogenates. Antiproteolytic activity of these substituted oxadiazole-2-thiones was reflected by their ability to inhibit trypsin hydrolysis of bovine serum albumin. These results indicated that the inhibition of cellular respiration and antiproteolytic activity of these substituted oxadiazole-2-thiones is not the biochemical basis for their anticonvulsant activity.
合成了8种5-(3,4-亚甲二氧基苯基)-3-芳基氨甲基-1,3,4-恶二唑-2-硫酮，通过其尖锐的熔点、元素分析和红外光谱对其进行了表征，并对其抗惊厥活性进行了评估。所有取代的恶二唑-2-硫酮都具有抗惊厥活性，这体现在它们在100 mg/kg腹腔注射时能为小鼠提供10% - 70%的保护，使其免受戊四氮诱导的惊厥。这些化合物在体外抑制了大鼠脑匀浆对烟酰胺腺嘌呤二核苷酸（NAD）依赖的丙酮酸、α-酮戊二酸和NADH的氧化，以及大鼠脑匀浆对琥珀酸的非NAD依赖氧化。这些取代的恶二唑-2-硫酮的抗蛋白水解活性体现在它们抑制胰蛋白酶对牛血清白蛋白水解的能力上。这些结果表明，这些取代的恶二唑-2-硫酮对细胞呼吸的抑制和抗蛋白水解活性并非其抗惊厥活性的生化基础。
