engleski

High throughput lipophilicity determination of novel macrolide inspired macrocycles

Currently, there is a large interest in macrocycles due to their structural uniqueness and high potential for difficult targets. In order to preserve favourable ADME properties of novel macrocyclic compounds, high-throughput chromatographic determination of lipophilicity and permeability parameters was used to monitor PhysChem properties. Standard computational tools for lipophilicity prediction are not applicable for 3D enriched macrocyclic compounds, therefore measured PhysChem data were used to guide design of novel compounds. Chromatographic Hydrophobicity Index by gradient reverse-phase HPLC was used at different pH values. An LC-MS system was used due to significant number of compounds lacking chromophores. The advantage of high-throughput PhysChem determination is the small amount of sample needed, which is favourable for the early stage of drug discovery.

Macrocycles; macrolides; lipophilicity

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