Restricted Diversity; Constrained Diversity-Oriented Synthesis

英国处于世界制药行业的前列，该行业开发治疗多种疾病的新药，并通过收入、就业、专业知识和重大投资使英国经济受益。英国制药业直接雇佣了大约7万名员工，通常为英国的GDP贡献100亿英镑。2007年的数据显示，该行业在英国的研发投资总额为39亿GB，英国的医药产品出口总额为146亿GB，医药产品贸易顺差为43亿GB。这是一个需要通过学术研究来支持的重要行业。该行业关注的是小分子的创造。药物是小分子药物。具有特定性质或功能的小分子的发现对将影响日常生活的科学进步显然是重要的。不幸的是，新药的开发存在一个严重的问题。由于临床候选人的高流失率，药物发现一直受到阻碍。这被归因于临床候选没有正确的性质或结合谱。这项建议旨在举例说明有效获取和发现与制药工业直接相关的所需性质或结合谱范围内的新的小分子的新策略。这一策略被称为受限的面向多样性的综合。该项目将涉及开发新的化学、合成新的小分子、区分评估受限的多样性以及发现具有生物活性的化合物和潜在的化疗药物。这一方法将为蛋白质相互作用调控作为化学生物学和分子治疗学工具的发展奠定科学和技术基础。这项拟议的工作有可能改变目前的药物发现方法，并从根本上扩展可用于化学生物学的工具。小分子对日常生活至关重要。它们的重要性超出了制药行业，因为塑料来自小分子，碳氢燃料是小分子，等等。因此，我们的研究有可能对健康和生活质量产生广泛影响。

The UK is at the forefront of the worldwide pharmaceutical industry, which develops new medicines for many diseases, and benefits the British economy through income, employment, expertise and major investment. The UK pharmaceutical industry directly employs around 70,000 people and typically contributes £10 billion to the UK's GDP. Figures for 2007 show that the industry invested a total of £3.9 billion in UK research and development, and that exports of pharmaceutical products from the UK totalled £14.6 billion, creating a trade surplus in pharmaceutical products of £4.3 billion. This is an important industry to support with academic research. The industry is concerned with the creation of small molecules. Pharmaceutical drugs are small molecules. The discovery of small molecules that have specific properties or functions is clearly important for scientific progress that will impact on everyday life. Unfortunately, there is a serious problem in the development of new drugs. Drug discovery has been hampered by a high rate of attrition of clinical candidates. This has been ascribed to the clinical candidates not having the correct properties or binding profiles.This proposal aims to exemplify new strategies to access efficiently and discover novel small molecules within a desired range of properties or binding profiles that are directly relevant to the pharmaceutical industry. This strategy has been termed constrained diversity-oriented synthesis. The project will involve the development of new chemistry, the synthesis of new small molecules, differential assessment of restricted diversity and the discovery of biologically active compounds and potential chemotherapeutic agents. The approach will lay the scientific and technological foundations for the development of protein-protein interaction modulation as a tool for chemical biology and molecular therapeutics. The proposed work has the potential to transform current approaches to drug discovery, and to radically extend the repertoire of tools available for chemical biology.Small molecules are essential to everyday life. They have importance beyond the pharmaceutical industry, since plastics derive from small molecules, hydrocarbon fuels are small molecules, etc. Therefore, our research has the potential to impact widely on health and quality of life.