苯并噻唑类衍生物的合成

由于杂环化合物具有广泛的生物活性,且具低毒、高效、对环境友好、结构多样化等多种优点,已成为当今药物开发的热点.以烟碱乙酰胆碱受体拮抗剂5-氯-2-苯并噁唑酮(商品名氯唑杀宗,chlorzoxazone)为先导,依据电子等排原理,将5-氯-2-苯并噁唑酮变换为以5-氯-2-苯并噻唑酮,设计了一系列5-氯-2-苯并噻唑酮衍生物,以期开发具有新型结构的烟碱乙酰胆碱受体拮抗剂.在合成方面,以4-氯-2-氨基苯硫醇为起始原料与脲素在酸性条件下闭环反应生成中间体5-氯-2-苯并噻唑酮,该中间体经重结晶纯化后,在碱性条件下,与一系列带有良好生物活性基团的卤代烃发生亲核取代,合成了六个未见文献报道的苯并噻唑衍生物,所有化合物均经过MS、1 H]NMR进行了结构表征,其生物活性有待研究.

Synthesis of benzothiazole derivatives

Heterocyclic compounds are becoming a research focus in drug development field with wide range of biological activity, low toxicity, high efficiency, environmental friendship and diverse structures. 5-chloro-2-benzoxazole ketone （chlorzoxazone） which is a nicotinic acetylcholine receptor antagonist was appliecl as a lead. The oxygen atom of the structure of 5-chloro-2-benzoxazole ketone was replaced by sulfur atom. Then a series of 5-chloro-2-benzothiazole derivatives were designed by the principle of bioisosterism and new structure of nicotinic acetylcholine receptor antagonists was developed. 5-chloro-2-benzothiazole ketones were synthesized by the reaction of 4-chloride-2-amino benzene mercaptan and urea, finally six phenylethanolamine benzothiazole derivatives were prepared followed by nucleophilic substitution with a series of halogenated hydrocarbon. All target compounds were characterized by 1HNMR, MS spectra. The biological activities of these compounds need further investigation.