Hi Dennis. I think there may be a misunderstanding. The EPSA means "exposed PSA" not experimental PSA. Please refer to the literature ACS Med. Chem. Lett. 2014, 5, 1167−1172; ACS Med. Chem. Lett. 2022, 13, 6, 964-971. As you mentioned, the intramolecular hydrogen bond of RMC-6291 may sheild the polarity of morpholine and amide, which results in a similar EPSA with compound 5
Thank you for your comment! In the original Pfizer paper(s), EPSA (an experimentally determined value from chromatography) was named EPSA in analogy to their previous experimental measure, ELogD (see AMCL 2014). While the "E" wasn't defined in the paper, many started to refer to this as experimental PSA and others exposed PSA, though people are all generally referring to this method.
