Praziquantel (PZQ) is the first line drug for the treatment of human Schistosoma spp. worm infections. However, it suffers from low activity towards immature stages of the worm, and its prolonged use induces resistance/tolerance. During the last 40 years, 263 PZQ analogues have been synthesized and tested against Schistosoma spp. worms, but less than 10% of them showed significant activity. Here, we propose a rationalization of the chemical space of the PZQ derivatives by a ligand-based approach. First, we constructed an in-house database with all PZQ derivatives available in the literature. This analysis shows a high heterogeneity in the data. Fortunately, all studies include PZQ as a reference, permitting the classification of compounds into three classes according to their activities. Models involving ligand-based pharmacophore and logistic regression were performed. Five physicochemical parameters were identified as the best to explain the biological activity. In the end, we proposed new PZQ derivatives with modifications at positions 1 and 7, we analysed them with our models, and we observed that they can be more active than the previously synthesized derivatives. The main goal of this work was to conduct the most valuable meta-pharmacometrics/pharmacoinformatics analysis with all Praziquantel medicinal chemistry data available in the literature.

吡喹酮（PZQ）是治疗人类血吸虫属的一线药物。蠕虫感染。但是，它对蠕虫未成熟阶段的活性较低，长时间使用会引起抗药性/耐受性。在过去的40年中，已经合成了263种PZQ类似物并针对血吸虫进行了测试spp。蠕虫，但只有不到10％表现出明显的活动。在这里，我们建议通过基于配体的方法合理化PZQ衍生物的化学空间。首先，我们建立了一个内部数据库，其中包含文献中所有可用的PZQ衍生物。该分析显示数据中的高度异质性。幸运的是，所有研究均以PZQ作为参考，从而允许根据化合物的活性将其分为三类。进行了涉及基于配体的药效团和逻辑回归的模型。确定了五个理化参数是解释生物学活性的最佳方法。最后，我们提出了在位置1和7进行了修改的新PZQ衍生物，并使用我们的模型对其进行了分析，我们发现它们比以前合成的衍生物更具活性。这项工作的主要目的是利用文献中提供的所有吡喹酮药物化学数据进行最有价值的元药理学/药物信息学分析。