In order to discover antiplatelet drugs with novel structures and expand our research scope, total twenty 1,3-benzenedisulfonyl piperazines, were designed and synthesized. These target compounds were divided into two series, namely 4-methoxy-1,3-benzenedisulfonyl piperazines of series 1 and 4-ethoxy-1,3-benzenedisulfonyl piperazines of series 2. With adenosine diphosphate (ADP), arachidonic acid (AA) and collagen as inducers, respectively, the Born turbidimetric method was used to screen the anti-platelet activity in vitro of all target compounds at a concentration of 1.3 μM, aspirin and picotamide as positive control drugs. And of which, the activity of five compounds for collagen was higher than both picotamide and aspirin. In ADP or AA channel, compounds with an inhibition rate greater than 33% were selected, and their corresponding IC₅₀ values were obtained. According to the IC₅₀, the in vitro activity of one compound for ADP was higher than picotamide, and for AA, two compounds were higher than two positive control drugs and other two compounds only higher than or equal to aspirin. Completed the preliminary analysis of the structure-activity relationship of the compound involved in this study. Further, eight compounds exhibiting the high activity in one or two test channels, were subjected to cytotoxicity test on mouse fibroblasts (L929) by CCK-8 method. The in vitro cytotoxicity of most test compounds showed less than or same to control drug picotamide at 10 μM, but at the higher concentration of 100 μM, merely two compounds exhibited higher cell survival rate than that of picotamide. In addition, compound N¹, N³-di (4-ethoxy-1, 3-benzenedisulfonyl)bis(1-(m-tolyl)piperazine), which is delivery activity in the three test channels, and compound N¹, N³- di (4-methoxy-1, 3-phenylenedisulfonyl)bis(1-(m-tolyl)piperazine), which is the lowest cytotoxic in vitro compound among series 1 and series 2, respectively, are found and selected for simulation analysis as two most likely to dock with the receptor P₂Y₁₂. Each of synthesized compounds in silico molecular property and ADME (absorption, distribution, metabolism and excretion) are predicted by using Molinspiration property engine v2018.10 and PreADMET online servers, respectively. Compared with other series of compounds in the previous stage, the two series compounds obtained after the introduction of piperazinyl have a similar in vitro activity.

为了发现结构新颖的抗血小板药物，扩大我们的研究范围，我们设计合成了20种1,3-苯二磺酰基哌嗪。这些目标化合物分为两大系列，即一系列4-甲氧基-1,3-苯二磺酰哌嗪1和4-乙氧基-1,3-苯二磺酰系列的哌嗪2. 分别以二磷酸腺苷（ADP）、花生四烯酸（AA）和胶原蛋白为诱导剂，采用Born比浊法筛选浓度为1.3 μM的所有目标化合物的体外抗血小板活性，阿司匹林和匹克胺为阳性控制药物。其中，5种化合物对胶原蛋白的活性高于匹克胺和阿司匹林。在ADP或AA通道中，选择抑制率大于33%的化合物，得到其相应的IC ₅₀值。根据 IC ₅₀, 一种化合物对 ADP 的体外活性高于匹克胺，对 AA 而言，两种化合物高于两种阳性对照药物，另两种化合物仅高于或等于阿司匹林。完成了对本研究涉及的化合物的构效关系的初步分析。此外，通过CCK-8方法对在一个或两个测试通道中表现出高活性的八种化合物进行了对小鼠成纤维细胞（L929）的细胞毒性测试。大多数测试化合物的体外细胞毒性在 10 μM 时表现出小于或等于对照药物匹克胺，但在 100 μM 的较高浓度下，只有两种化合物表现出比匹克胺更高的细胞存活率。此外，化合物N ¹、N ³-di (4-ethoxy-1, 3-benzodisulfonyl)bis(1-(m-tolyl)piperazine)，这是三个测试通道中的传递活性，以及​​化合物N ¹ , N ³ - di (4-methoxy-1) , 分别是系列1和系列2中体外细胞毒性最低的化合物 3-苯二磺酰基)双 (1-(间甲苯基)哌嗪)被发现并选择进行模拟分析作为最有可能与受体对接的两种P ₂ Y ₁₂. 分别使用 Molinspiration 属性引擎 v2018.10 和 PreADMET 在线服务器预测每个合成化合物的 silico 分子特性和 ADME（吸收、分布、代谢和排泄）。与前一阶段的其他系列化合物相比，引入哌嗪基后得到的两个系列化合物具有相似的体外活性。