Accurate prediction of K based on experimental measurement of K and computed physicochemical properties of candidate compounds in CNS drug discovery.

A mathematical equation model was developed by building the relationship between the f/f ratio and the computed physicochemical properties of candidate compounds, thereby predicting K based on a single experimentally measured K value. A total of 256 compounds and 36 marketed published drugs including acidic, basic, neutral, zwitterionic, CNS-penetrant, and non-CNS penetrant compounds with diverse structures and physicochemical properties were involved in this study. A strong correlation was demonstrated between the f/f ratio and physicochemical parameters (CLogP and ionized fraction).