Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA.
The Broad Institute of Harvard & MIT, Cambridge, MA, USA.
Nat Rev Drug Discov. 2018 May;17(5):333-352. doi: 10.1038/nrd.2018.53. Epub 2018 Apr 13.
Screening of small-molecule libraries is a productive method for identifying both chemical probes of disease-related targets and potential starting points for drug discovery. In this article, we focus on strategies such as diversity-oriented synthesis that aim to explore novel areas of chemical space efficiently by populating small-molecule libraries with compounds containing structural features that are typically under-represented in commercially available screening collections. Drawing from more than a decade's worth of examples, we highlight how the design and synthesis of such libraries have been enabled by modern synthetic chemistry, and we illustrate the impact of the resultant chemical probes and drug leads in a wide range of diseases.
小分子文库筛选是一种富有成效的方法，可用于鉴定与疾病相关靶标相关的化学探针和潜在的药物发现起点。在本文中，我们重点介绍了多样性导向合成等策略，这些策略旨在通过用通常在商业可用筛选集中代表性不足的结构特征化合物来填充小分子文库，从而有效地探索新的化学空间领域。通过十多年的例子，我们强调了现代合成化学如何使这些文库的设计和合成成为可能，并说明了广泛疾病中这些化学探针和药物先导物的影响。
