Separation and Analysis Technology Team, Bristol Myers Squibb, Lawrenceville, NJ, USA.
Chemotype Discovery and Optimization, Bristol Myers Squibb, Lawrenceville, NJ, USA.
Chem Commun (Camb). 2021 Oct 21;57(84):11037-11040. doi: 10.1039/d1cc03791a.
In recent years, successful assay miniaturization has enabled the exploration of synthesis scale reduction in pharmaceutical discovery. Miniaturization of pharmaceutical synthesis and purification allows a reduction in material consumption and shortens timelines, which ultimately reduces the cost per experiment without compromising data quality. Isolating and purifying the compounds of interest is a key step in the library synthesis process. In this manuscript we describe a high-throughput purification workflow in support of microscale (1-5 μmol or 0.5-2 mg) library synthesis. The optimized microscale purification system can routinely purify 384-well reaction plates with an analysis time of 4 min per sample. Instrument optimization, critical parameters such as column loading, delay time calibration, ultrafast pre- and post-purification analysis and library purification examples are provided.
近年来，成功的分析微型化使得人们能够探索制药发现中合成规模的缩小。药物合成和纯化的微型化可以减少材料消耗并缩短时间线，从而在不影响数据质量的情况下降低每个实验的成本。分离和纯化感兴趣的化合物是文库合成过程中的关键步骤。在本文中，我们描述了一种高通量纯化工作流程，以支持微尺度（1-5 μmol 或 0.5-2 mg）文库合成。优化的微尺度纯化系统可以常规地纯化 384 孔反应板，每个样品的分析时间为 4 分钟。提供了仪器优化、柱上样、延迟时间校准、超快预纯化和后纯化分析以及文库纯化实例等关键参数。
