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（通常为氮、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。许多种类的天然产物，以及大多数商业上重要的药物、农用化学品、营养材料、染料等，含有杂环。因此，杂环化合物，特别是含氮环的合成和研究对于学术界和工业界都是非常重要的课题。杂环化合物的商业相关性通过最畅销的药物列表充分证明。在截至2005年6月的12个月里，前十名最畅销的产品中有七种是氮杂环化合物，总销售额为410亿美元（前十名为557亿美元）。该提案得到了GSK的全力支持，旨在寻求支持开发一些新方法，以有效和快速地在实验室制备作为潜在药物的杂环分子阵列。阵列是一组化合物，通常通过自动化方法同时制备，其中分子的结构组分系统地变化。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.