Abbott Products GmbH, Unit Chemical Design and Synthesis, Hannover, Germany.
J Sep Sci. 2011 Nov;34(21):2983-8. doi: 10.1002/jssc.201100382. Epub 2011 Oct 14.
Automated medicinal chemistry (parallel chemistry) has become an integral part of the drug-discovery process in almost every large pharmaceutical company. Parallel array synthesis of individual organic compounds has been used extensively to generate diverse structural libraries to support different phases of the drug-discovery process, such as hit-to-lead, lead finding, or lead optimization. In order to guarantee effective project support, efficiency in the production of compound libraries has been maximized. As a consequence, also throughput in chromatographic purification and analysis has been adapted. As a recent trend, more laboratories are preparing smaller, yet more focused libraries with even increasing demands towards quality, i.e. optimal purity and unambiguous confirmation of identity. This paper presents an automated approach how to combine effective purification and structural conformation of a lead optimization library created by microwave-assisted organic synthesis. The results of complementary analytical techniques such as UHPLC-HRMS and NMR are not only regarded but even merged for fast and easy decision making, providing optimal quality of compound stock. In comparison with the previous procedures, throughput times are at least four times faster, while compound consumption could be decreased more than threefold.
自动化药物化学（平行化学）已成为几乎每家大型制药公司药物发现过程的一个组成部分。已经广泛使用单个有机化合物的平行排列合成来生成不同的结构库，以支持药物发现过程的不同阶段，如命中到先导化合物、先导化合物发现或先导化合物优化。为了保证有效的项目支持，化合物库的生产效率已被最大化。因此，色谱纯化和分析的通量也进行了调整。最近的一个趋势是，更多的实验室正在准备更小但更集中的库，同时对质量的要求更高，即最佳纯度和身份的明确确认。本文提出了一种自动化方法，用于结合通过微波辅助有机合成创建的先导化合物优化库的有效纯化和结构构象。互补分析技术（如 UHPLC-HRMS 和 NMR）的结果不仅被考虑，而且甚至被合并用于快速轻松地做出决策，从而提供化合物库存的最佳质量。与以前的程序相比，通量时间至少快四倍，而化合物消耗可以减少三倍以上。
