The discovery of bioactive compounds underpins many areas of basic biomedical research and constitutes a large part of medicinal chemistry and chemical biology. Synthetic chemistry is now able to provide almost any drug-like molecule imaginable. Therefore, attention has turned to increasing the biological relevance of the compounds to be used in chemical biology and medicinal chemistry research, as well as maximizing their diversity within this large area of chemical space. In this review, we outline key concepts for the design of biologically relevant compound collections by taking inspiration from nature and natural products. We highlight efficient ways to screen the resulting libraries in order to maximize hit rates and the chance of discovering new modes of action. Finally, we discuss state-of-the-art techniques for the identification of molecular targets of hits identified through phenotypic screening approaches.

生物活性化合物的发现奠定了基础生物医学研究的许多领域，并构成了药物化学和化学生物学的很大一部分。合成化学现在能够提供几乎可以想象到的任何药物样分子。因此，注意力已转移到增加将用于化学生物学和药物化学研究的化合物的生物学相关性，以及最大程度地扩大其在该大化学空间区域内的多样性。在这篇综述中，我们从自然和天然产物中汲取灵感，概述了生物相关化合物集合设计的关键概念。我们重点介绍了有效的方法来筛选生成的库，以最大程度地提高命中率和发现新的操作模式的机会。最后，