Cashman J R, Parikh K K, Traiger G J, Hanzlik R P
Chem Biol Interact. 1983 Aug 1;45(3):341-7. doi: 10.1016/0009-2797(83)90080-7.
Thiobenzamide is known to be hepatotoxic in the rat and the relative hepatotoxicity of para-substituted thiobenzamides has previously been shown to depend strictly on the electronic character of the para substituent. We have now extended this study to include ortho and meta monosubstituted thiobenzamides. Among the meta-substituted compounds, hepatotoxicity varies in strict accordance with the electronic character of the substituent, whereas the ortho-substituted compounds show no toxicity at comparable doses regardless of the nature of the substituent. Explanations for these substituent effects are provided in terms of the chemical reactivity of the compounds and their corresponding S-oxide and S,S-dioxide metabolites.
已知硫代苯甲酰胺对大鼠具有肝毒性，先前已表明对位取代硫代苯甲酰胺的相对肝毒性严格取决于对位取代基的电子特性。我们现在已将这项研究扩展至包括邻位和间位单取代硫代苯甲酰胺。在间位取代化合物中，肝毒性严格按照取代基的电子特性而变化，而邻位取代化合物在相当剂量下无论取代基的性质如何均无毒性。根据这些化合物及其相应的S-氧化物和S,S-二氧化物代谢物的化学反应性对这些取代基效应作出了解释。
