Transition-Metal-Catalysed Cycloaddition Methodology for the Convergent Assembly of (Hetero)Aromatic Compounds

制药业继续开发新药是改善和维持人类健康的一项重要努力，对社会的相关惠益是显而易见的。为了开发新药，药物化学家必须准备大量不同的化合物，以确定一个有希望的命中，然后采取进一步的发展，在生产进一步的化合物集合。因此，正如人们所想象的，用于制备这些化合物的方法（化学反应）必须非常有效、可靠和通用。尽管已知大量的化学反应（数量每天都在持续增长），但这些反应中只有非常小的一部分适合用于制备这些化合物库。这是因为大多数反应不能满足在化合物文库的生成中应用的一个或多个苛刻标准列表。例如，许多反应仅适用于狭窄的有限范围的情况，或者它们需要使用外来试剂或不方便的反应条件。这一限制因素为有效开发新药提供了强大的障碍。拟议的研究旨在开发一种早已为人所知，但在制药工业中很少被药物化学家使用的反应。该反应采用过渡金属催化剂来促进几个反应伙伴之间的反应，以生成在药物和药物样分子中突出的环状分子。我们将开发专门针对药物化学家要求的通用方法的新变体，并修改目前不太符合这些要求的现有方法。我们期望我们可以取得许多进展，积极影响药物发现的过程，开发有价值的（和可重复的）化学沿着。这项研究将由爱丁堡大学和葛兰素史克的博士后研究助理共同进行，他们将获得最先进的设备。

The continued development of new medicines by the pharmaceutical industry is a critical endeavour to improve and maintain human health, and the associated benefits to society are obvious. In order to develop new drugs, pharmaceutical chemists must prepare large collections of diverse compounds in order to identify a promising hit , which is then taken on for further development in the production of further collections of compounds. Therefore, as one might imagine, the methods (chemical reactions) which are used to prepare these compounds must be very efficient, reliable, and general in nature.Although a huge number of chemical reactions are known, (a number that continues to grow on a daily basis), only a very small proportion of these reactions are suitable for use in the preparation of these compound libraries. This is because most reactions fail to meet one or more of a list of demanding criteria that are applied in the generation of compound libraries. For example, many reactions only work for a narrow, restricted range of cases, or they require the use of exotic reagents or inconvenient reaction conditions. This limiting factor provides a powerful obstacle to the efficient development of new medicines.The proposed research is aimed at developing a reaction that has been known for a long time, but is rarely used by medicinal chemists in the pharmaceutical industry. This reaction employs a transition-metal catalyst to promote the reaction between several reaction partners to generate cyclic molecules that feature prominently in drugs and drug-like molecules. We will develop new variants of the general methodologies specifically targeted at the requirements of medicinal chemists, as well as modifying existing methodologies that currently do not quite fit these requirements. We anticipate that we can make numerous advances to positively impact the process of drug discovery, developing valuable (and publishable) chemistries along the way.This research will be conducted by a postdoctoral research associate working jointly at the University of Edinburgh and at GlaxoSmithKline, where they will have access to state-of-the-art equipment.