Multiple computer-automated structure evaluation model of the plasma protein binding affinity of diverse drugs

摘要

A drug protein binding model was constructed on the basis of protein-affinity data for 154 drugs. The Multiple Computer-Automated Structure Evaluation program (M-CASE) was used for the construction of the model, which separates the total data set into groups of drugs with common structural features. For each of these groups, a multiparameter Quantitative Structure-Activity Relationship (QSAR) was obtained. The most general structural fragment for all investigated drugs is a part of the phenyl ring. The lipophilicity represented by the octanol-water partition coefficient was also found to be a significant parameter for each local QSAR. The model was shown to be able to predict correctly the percentage of drug bound in plasma for ～80% of compounds with an average error of only ～14%.