Development of new protocols for the synthesis of arrays of heterocycles

杂环化合物，其中一个或多个碳原子被杂原子(通常是氮、氧或硫)取代的环状分子占所有已知有机化合物的一半以上。许多种类的天然产品以及大多数具有重要商业价值的药物、农用化学品、复制材料、染料等都含有杂环。因此，杂环化合物的合成和研究，特别是含氮环化合物的合成和研究，对学术界和工业界都具有极其重要的意义。杂环化合物的商业相关性从畅销药品名单中得到了充分的证明。在截至2005年6月的12个月里，前十大畅销书中有七个是氮杂环化合物，总销售额为410亿美元(前十名的总销售额为557亿美元)。这一提议得到了葛兰素史克的全力支持，旨在为开发一些新的方法提供支持，以便在实验室有效和快速地制备作为潜在药物的杂环分子阵列。阵列是一组化合物，通常由自动化方法同时制备，其中分子的结构成分是系统地变化的。虽然阵列合成是现代药物化学中的基本工具，但可以使用的反应仍然有些有限，因此迫切需要寻找新的方法和方案。

Heterocyclic compounds, cyclic molecules in which one or more carbon atom is replaced by a heteroatom (commonly nitrogen, oxygen or sulfur) account for well over half of all known organic compounds. Many classes of natural products, as well as a large majority of commercially important drugs, agrochemicals, reprographic materials, dyes, etc., contain heterocyclic rings. Hence the synthesis and study of heterocyclic compounds, in particular nitrogen containing rings, is a subject of immense importance both for academia and industry. The commercial relevance of heterocyclic compounds is amply demonstrated by the list of best selling pharmaceuticals. In the 12 months to June 2005, seven of the top ten best sellers were nitrogen heterocycles with combined sales of $41 billion (out of $55.7 billion for the top ten). This proposal, which has the full support of GSK, seeks support to develop some new methods for the efficient and rapid laboratory preparation of arrays of heterocyclic molecules as potential medicines. Arrays are sets of compounds, usually prepared simultaneously by automated methods, where structural components of the molecule are varied systematically. Although array synthesis is a fundamental tool in modern medicinal chemistry, the reactions that can be used remain somewhat limited, and therefore new methods and protocols are urgently sought.