Relative hepatotoxicity of ortho and meta mono substituted thiobenzamides in the rat |
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Authors: | John R. Cashman Ketankumar K. Parikh George J. Traiger Robert P. Hanzlik |
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Affiliation: | 1. Department of Medicinal Chemistry, University of Kansas, Lawrence, KS 66045 U.S.A.;2. Department of Pharmacology and Toxicology, University of Kansas, Lawrence, KS 66045 U.S.A. |
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Abstract: | 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. |
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Keywords: | Thiocarbonyl compounds Thiobenzamide Hepatotoxicity To whom correspondence should be sent. |
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