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护人类健康的一项重要努力，相关的社会利益是显而易见的。为了开发新药，药物化学家必须准备大量不同的化合物集合，以确定有希望的热门药物，然后在生产更多化合物集合的过程中进行进一步开发。因此，正如人们可以想象的那样，用于制备这些化合物的方法(化学反应)必须是非常高效、可靠和通用的。尽管已知了大量的化学反应(数量每天都在继续增加)，但这些反应中只有很小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化合物文库生成中应用的一个或多个要求严格的标准。例如，许多反应只适用于狭窄、有限的情况，或者它们需要使用外来试剂或不方便的反应条件。这一限制因素为新药的高效开发提供了强大的障碍。拟议的研究旨在开发一种早已为人所知但很少被制药行业的药物化学家使用的反应。该反应使用过渡金属催化剂来促进几个反应伙伴之间的反应，以生成在药物和类药物分子中突出表现的环状分子。我们将开发专门针对药物化学家要求的一般方法的新变体，以及修改目前不太符合这些要求的现有方法。我们预计，我们可以取得许多进展，对药物发现过程产生积极影响，在此过程中开发有价值的(和可发表的)化学物质。这项研究将由爱丁堡大学和葛兰素史克公司的博士后助理进行，他们将在那里获得最先进的设备。

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.