Synthesis and Antithyroid Activity of Pyridine, Pyrimidine and Pyrazine Derivatives of Thiazole-2-thiol and 2-Thiazoline-2-thiol.
作者:Jean-Francois LAGORCE、Francis COMBY、Annick ROUSSEAU、Jacques BUXERAUD、Claude RABY
DOI:10.1248/cpb.41.1258
日期:——
A series of compounds was synthesized by linking various derivatives of pyridine, pyrimidine or pyrazine to thiazole-2-thiol or to its partially hydrogenated derivative 2-thiazoline-2-thiol. The reactions of the compounds with molecular iodine and lactoperoxidase were examined in vitro. Their antithyroid activity was also examined in vivo in the rat. T4 and TSH levels were determined, and the thyroid gland was examined histologically. 2-(3-Hydroxy-2-pyridyl)-2-thiothiazoline had the highest antithyroid activity of the compounds tested (Kc=14931·mol-1, IC500.65×10-4M, activity of thryoid gland +++).
通过将吡啶、嘧啶或吡嗪的各种衍生物与噻唑-2-硫醇或其部分氢化衍生物 2-噻唑啉-2-硫醇连接,合成了一系列化合物。体外研究了这些化合物与分子碘和乳过氧化物酶的反应。还在大鼠体内检测了它们的抗甲状腺活性。测定了 T4 和 TSH 水平,并对甲状腺进行了组织学检查。在所测试的化合物中,2-(3-羟基-2-吡啶基)-2-噻唑啉的抗甲状腺活性最高(Kc=14931-mol-1,IC500.65×10-4M,甲状腺活性 +++)。