In Vivo Biological Activity of Antioxidative Aminothiazole Derivatives

概要

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For the development of novel antioxidants having therapeutic utility, a new series of condensed 4- and 5-aminothiazole derivatives has been synthesized using simple methods. Condensed 4-aminothiazoles were prepared by the reaction of α-bromolactams with thioamides in ethanol and 5-aminothiazole derivatives were obtained by the treatment of 3-(acylamino)lactams with a thiating agent such as phosphorus pentasulfide and Lawesson's reagent in pyridine. In vitro assay of the condensed 5-aminothiazole derivatives showed them to be potent inhibitors of lipid peroxidation. In order to evaluate these compounds in an in vivo system, we devised a simple and reproducible method in which the inhibition of characteristic behaviors induced by spinal injection of FeCl_2 was expressed numerically. Compounds having strong in vitro activity protected the central nervous system from injury caused by iron-dependent lipid peroxidation. The results suggest that the in vivo assay developed in this study should be useful as a screening method for antioxidants and also that condensed 5-aminothiazole derivatives are promising candidates for the treatment of traumatic and ischemic injury of the central nervous system.
公益社団法人日本薬学会の論文
1996-11-15