依据药物作用的靶分子结构进行新药设计，作为药物研究中的新方法使新药的研发过程正在从一种偶然性、经验性的过程逐渐走向一种合理的、科学的研发过程。作者在结合国内外有关文献基础上对这一方法的基本原理和基本过程进行综述。

American trypanosomiasis, or Chagas' disease, is the leading cause of heart disease in Latin America. Currently there is an urgent need to develop antitrypanosomal therapy due to the toxicity of existing agents and emerging drug resistance. A novel series of potent thio semicarbazone small-molecule inhibitors of the Trypanosoma cruzi cysteine protease cruzain have been identified. Some of these inhibitors have been shown to be trypanocidal. We initially discovered that 3¢-bromopropiophenone thio semicarbazone (1i) inhibited cruzain and could cure mammalian cell cultures infected with T. cruzi. 3¢-Bromopropiophenone thio semicarbazone showed no toxicity for mammalian cells at concentrations that were trypanocidal. Following this lead, more than 100 compounds were designed and synthesized. A specific structureactivity relationship (SAR) was established, and many potent analogues with IC50 values in the low nanomolar range were identified. Eight additional analogues were trypanocidal in a cell culture assay, and this indicates that aryl thio semicarbazone is a productive scaffold for killing the parasites. Kinetic studies show that these are time-dependent inhibitors. Molecular modeling studies of the enzyme-inhibitor complex have led to a proposed mechanism of interaction as well as insight into the SAR of the thio semicarbazone series. The nonpeptide nature of this series, small size, and extremely low cost of production suggest this is a promising direction for the development of new antitrypanosome chemotherapy.

以苄胺和丙烯酸甲酯为起始原料，全成OPC-21268的重要中间体1-苄基-4-哌淀酮，并对每步反应的工艺进行优化，确定了最佳反应条件，三步反应的总收率为74.5%，比文献值提高了14.5%。新工艺做法简单，成本降低，适于工业生产。

目的：设计合成3-溴-4-硫色（满）酮类化合物，并对基抗真菌活性进行初步评价。方法：以取代硫色（满）酮原料，经漠化、氧化等反应制得目标化合物，化合物体外抗真菌活性测定采用二倍浓度稀释法。结果：共合成了9个未见文献报道的新化合物，经红外光谱、核磁共振氢谱及元素分析确证其结构。其中化合物Vb的活性好于或相当于对照品药。结论：梳色（满）酮3-漠取代后其有较强的抗真菌活性。

目的：设计合成3-次苄基硫色满酮类化合物，并对基抗真菌活性进行初步评价。方法：以取代苯硫酚为原料，经多步反应制得目标化合物，并采用琼脂2倍浓度稀释法测定目标谷物的抗真菌活性。结果：共合成了6个新化合物，经红外光谱、核磁共振氢谱及元素分析确证其结构。目标化合物对大部分供试真菌具有活性，但弱于对照品克霉唑。结论：3-次苄基硫色满酮在体外具有一定的抗真菌活性。