水友相互作用液体色谱的新应用,用于识别具有分子内键的化合物
Alessandra Pugliano1, Bernd Kuhn1, Nenad Manevski1
1Roche Pharmaceutical Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, Basel CH-4070, Switzerland.
Journal of pharmaceutical and biomedical analysis
|October 17, 2024
概括
这项研究引入了一种新的色谱方法,使用水友相互作用液体色谱 (HILIC) 来识别候选药物中的分子内键 (IMHB). 这种技术有助于优化分子,在早期药物发现过程中提高溶解度和生物可用性.
科学领域:
- 药用化学 医学化学
- 分析化学 分析化学
- 计算化学的计算化学
背景情况:
- 内分子键 (IMHB) 增强药物候选物质的特性,如溶解性和透性.
- 传统的IMHB检测方法 (光谱,衍射) 缺乏用于早期药物发现查的吞吐量.
- 超临界流体染色学 (SFC) 已经显示出潜在的间接IMHB识别.
研究的目的:
- 为IMHB评估开发一种基于高性能液体染色体质谱法 (HPLC-MS) 的方法.
- 为了建立一个染色学参数来评估化合物对IMHB形成的倾向.
- 为现有的IMHB检测技术提供可扩展的替代方案.
主要方法:
- 探索水友互动液体色谱 (HILIC) 用于化合物分离.
- 基于保留数据的结驱动吸附 (kads) 参数的开发.
- 使用匹配的分子对 (MMP) 分析和量子力学计算对形状数据.
主要成果:
- 一种新的染色学方法有效地根据键特性区分化合物.
- 该kads参数量化一个化合物形成IMHB的倾向.
- 该kads参数成功地分化了形成IMHB的分析物,而不需要控制化合物.
结论:
- 开发的HILIC-MS方法为IMHB在药物发现中的评估提供了一种可行的染色学方法.
- 该kads参数提供了IMHB倾向的可靠测量,有助于击中化合物选.
- 这种方法提高了识别具有改善物理化学性质的候选药物的效率.
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