Laboratory of Medicinal and Advanced Synthetic Chemistry (Lab MASC), Department of Pharmaceutical Sciences, University of Perugia, Via del Liceo 1, 06123 Perugia, Italy.
J Med Chem. 2020 Jul 9;63(13):6624-6647. doi: 10.1021/acs.jmedchem.9b01956. Epub 2020 Feb 21.
Medicinal chemistry plays a fundamental and underlying role in chemical biology, pharmacology, and medicine to discover safe and efficacious drugs. Small molecule medicinal chemistry relies on iterative learning cycles composed of compound design, synthesis, testing, and data analysis to provide new chemical probes and lead compounds for novel and druggable targets. Using traditional approaches, the time from hypothesis to obtaining the results can be protracted, thus limiting the number of compounds that can be advanced into clinical studies. This challenge can be tackled with the recourse of enabling technologies that are showing great potential in improving the drug discovery process. In this Perspective, we highlight recent developments toward innovative medicinal chemistry strategies based on continuous flow systems coupled with automation and bioassays. After a discussion of the aims and concepts, we describe equipment and representative examples of automated flow systems and end-to-end prototypes realized to expedite medicinal chemistry discovery cycles.
药物化学在化学生物学、药理学和医学中起着基础性和基础性的作用，以发现安全有效的药物。小分子药物化学依赖于由化合物设计、合成、测试和数据分析组成的迭代学习循环，为新的和可成药的靶标提供新的化学探针和先导化合物。使用传统方法，从假设到获得结果的时间可能会延长，从而限制了可以推进到临床研究的化合物数量。这一挑战可以通过利用具有巨大潜力的使能技术来解决，这些技术正在改善药物发现过程。在本观点中，我们重点介绍了基于连续流系统与自动化和生物测定相结合的创新药物化学策略的最新进展。在讨论了目标和概念之后，我们描述了实现加速药物化学发现周期的自动化流系统和端到端原型的设备和代表性实例。
