Respiratory CEDD, GlaxoSmithKline, Gunnels Wood Road, Stevenage, SG1 2NY, UK.
Angew Chem Int Ed Engl. 2010 Oct 25;49(44):8082-91. doi: 10.1002/anie.201002238.
Synthetic organic reactions are a fundamental enabler of small-molecule drug discovery, and the vast majority of medicinal chemists are initially trained--either at universities or within industry--as synthetic organic chemists. The sheer breadth of synthetic methodology available to the medicinal chemist represents an almost endless source of innovation. But what reactions do medicinal chemists use in drug discovery? And what criteria do they use in selecting synthetic methodology? Why are arrays (small focused libraries) so powerful in the lead-optimization process? In this Minireview, we suggest some answers to these questions and also describe how we have tried to expand the number of robust reactions available to the medicinal chemist.
合成有机反应是小分子药物发现的基础，绝大多数药物化学家最初都是在大学或工业界接受合成有机化学方面的培训。药物化学家可利用的合成方法学非常广泛，这几乎为创新提供了无尽的源泉。但是，药物化学家在药物发现中使用哪些反应？他们在选择合成方法学方面使用哪些标准？为什么在先导化合物优化过程中，组合库（小而聚焦的文库）如此强大？在这篇综述中，我们对这些问题提出了一些答案，并描述了我们如何尝试扩大可供药物化学家使用的稳健反应数量。
