School of Chemistry and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, LS2 9JT, UK.
Rosalind Franklin Institute, Harwell Campus, Didcot, OX11 0FA, UK.
ChemMedChem. 2020 Oct 5;15(19):1776-1782. doi: 10.1002/cmdc.202000524. Epub 2020 Sep 4.
Activity-directed synthesis (ADS) is a structure-blind, functional-driven molecular discovery approach. In this Concept, four case studies highlight the general applicability of ADS and showcase its flexibility to support different medicinal chemistry strategies. ADS deliberately harnesses reactions with multiple possible outcomes, and allows many chemotypes to be evaluated in parallel. Resources are focused on bioactive molecules, which emerge in tandem with associated synthetic routes. Some of the future challenges for ADS are highlighted, including the realisation of an autonomous molecular discovery platform. The prospects for ADS to become a mainstream lead generation approach are discussed.
活性导向合成（ADS）是一种结构盲、功能驱动的分子发现方法。在这个概念中，四个案例研究强调了 ADS 的普遍适用性，并展示了其支持不同药物化学策略的灵活性。ADS 故意利用具有多种可能结果的反应，并允许许多化学型同时进行评估。资源集中在具有生物活性的分子上，这些分子与相关的合成途径一起出现。还强调了 ADS 的一些未来挑战，包括实现自主分子发现平台。讨论了 ADS 成为主流先导化合物生成方法的前景。
