The key objectives of medicinal chemistry are to efficiently design and synthesize bioactive compounds that have the potential to become safe and efficacious drugs. Most medicinal chemistry programmes rely on screening compound collections populated by a range of molecules derived from a set of known and robust chemistry reactions. Analysis of the role of synthetic organic chemistry in subsequent hit and lead optimization efforts suggests that only a few reactions dominate. Thus, the uptake of new synthetic methodologies in drug discovery is limited. Starting from the known limitations of reaction parameters, synthesis design tools, synthetic strategies and innovative chemistries, here we highlight opportunities for the expansion of the medicinal chemists' synthetic toolbox. More intense crosstalk between synthetic and medicinal chemists in industry and academia should enable enhanced impact of new methodologies in future drug discovery.

药物化学的关键目标是有效设计和合成具有成为安全有效药物潜力的生物活性化合物。大多数药物化学程序都依赖于筛选由一系列已知和可靠的化学反应衍生的一系列分子组成的化合物集合。对合成有机化学在随后的命中和线索优化工作中的作用的分析表明，只有少数反应占主导。因此，在药物发现中采用新的合成方法受到了限制。从反应参数，合成设计工具，合成策略和创新化学方法的已知局限性出发，我们在这里着重介绍扩大药物化学家的合成工具箱的机会。