芳酰基硫脲类克鲁斯氏锥体虫半胱氨酸蛋白酶小分子抑制剂的合成及活性研究

目的：通过设计、合成芳酰基硫脲类化合物发现新的克鲁斯氏锥体虫半胱氨酸蛋白酶小分子抑制剂。方法：通过芳酰基硫代异氰酸酯和取代苯胺的反应合成芳酰基硫脲类化合物，化合物的结构经HRMS(EI)和^1H-NMR光谱确证。结果：共合成了20个芳酰基硫脲类化合物，化合物的体外抑制克鲁斯氏锥体虫半胱氨酸蛋白酶的活性测定结果表明：所合成的化合物均有一定的抑制克鲁斯氏锥体虫半胱氨酸蛋白酶的活性，其中化合物Id和In的活性高于对照药tf-175的活性。结论：这类化合物有可能开发成新的抗南美锥体虫病的化疗药物。

Synthesis of the aroyl thiourea derivatives as novel small molecule inhibitors of cysteine protease of Trypanosomal cruzi

Aim New aroyl thiourea derivatives were designed and synthesized in order to find novel small molecule inhibitors of cysteine protease of T.cruzi. Method A series of aroyl thiourea derivatives was prepared from corresponding aroyl isothiocynates and substituted anilines.The chemical structures of these compounds were characterized by HRMS(EI)and 1H NMR spectroscopy.Results The total 20 compounds of aroyl thiourea derivatives were synthesized.The results of the bioassay in vitro against cruzain showed that all the synthesized compounds exhibited certain activity,among which compounds Id and In were more active than the control inhibitor tf 175.Conclusion This class of inhibitors might be probably developed to be a new type of candidates for antitrypanosomal chemotherapy.