EPSA(Exposed Polar Surface Area), as a supercritical fluid chromatography technique, has been used in detecting the intra-molecular hydrogen bonds in small molecules and designing design orally permeable peptides. However, only qualitative correlation between EPSA and permeability has been reported in the literature. In this study, we have applied EPSA on compounds from one current project and observed an exceptionally good correlation between EPSA and the apparent permeability and intrinsic permeability measured by Caco-2 within the lead series compounds. None of the other measured or calculated physical properties have comparable correlation with measured permeability. Here we analyzed the features of this set of molecules and used them to explain the correlation. In addition, since EPSA is much faster and cheaper than Caco-2 assay, we have used EPSA as a surrogate assay for permeability in guiding the compound design and selection.<br/>

Applying EPSA in guiding permeability optimization of small molecules

255th National Meeting (2018)

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