Department of Chemistry, University of Michigan, Ann Arbor, MI 48109, USA.
Global Discovery Chemistry, Novartis Institutes for Biomedical Research, Cambridge, MA 02139, USA.
Angew Chem Int Ed Engl. 2023 Jul 10;62(28):e202301664. doi: 10.1002/anie.202301664. Epub 2023 Apr 18.
Within the realm of drug discovery, high-throughput experimentation techniques enable the rapid optimization of reactions and expedited generation of drug compound libraries for biological and pharmacokinetic evaluation. Herein we report the development of a segmented flow mass spectrometry-based platform to enable the rapid exploration of photoredox reactions for early-stage drug discovery. Specifically, microwell plate-based photochemical reaction screens were reformatted to segmented flow format to enable delivery to nanoelectrospray ionization-mass spectrometry analysis. This approach was demonstrated for the late-stage modification of complex drug scaffolds, as well as the subsequent structure-activity relationship evaluation of synthesized analogs. This technology is anticipated to expand the robust capabilities of photoredox catalysis in drug discovery by enabling high-throughput library diversification.
在药物发现领域，高通量实验技术能够实现反应的快速优化，并加速药物化合物库的生成，以便进行生物学和药代动力学评估。在此，我们报告了一种基于分段流动质谱的平台的开发，该平台可用于快速探索光氧化还原反应，以用于早期药物发现。具体而言，我们将微孔板基光化学反应筛选重新格式化到分段流动格式，以实现递送至纳升电喷雾电离-质谱分析。该方法已用于复杂药物支架的后期修饰，以及随后合成类似物的构效关系评估。该技术有望通过实现高通量库多样化，扩展光氧化还原催化在药物发现中的强大功能。
