Accurate prediction of K_p,uu,brain based on experimental measurement of K_p,brain and computed physicochemical properties of candidate compounds in CNS drug discovery.

ABSTRACT: A mathematical equation model was developed by building the relationship between the f_u,b/f_u,p ratio and the computed physicochemical properties of candidate compounds, thereby predicting K_p,uu,brain based on a single experimentally measured K_p,brain 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_u,b/f_u,p ratio and physicochemical parameters (CLogP and ionized fraction). The model showed good performance in both internal and external validations. The percentages of compounds with K<

SUBMITTER: Ma Y 

PROVIDER: S-EPMC10828645 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature