Ранжированный ряд фрагментов молекул лекарственных средств, определяющих их нейродоступность

By using computer modeling methods based on the quantitative structure – property relationships (QSPRs), it is possible both to perform rational planning of experimental researches and carry out the effective generation of structures able to permeate through the blood-brain barrier (BBB). This work was aimed at (i) the creation of QSPR models based on the simplex representation of molecules for nonexperimental estimation of their ability to permeate the BBB and (ii) structural interpretation of the proposed models with allowance for the mutual influence of atoms in molecules. Based on the simplex representation of molecular structure, the contribution of various fragments and functional groups to the neuroavailability was estimated. In particular, it was found that the presence of highly polar groups (carboxyl, carbonyl, phenolic hydroxyl) has negative influence on the ability of molecule to enter the brain. The presence of halogen atoms and aromatic fragments positively influence the efficacy of transfer through the BBB. The formulated QSPR model possesses satisfactory prognostic ability that has been estimated using the RandomForest internal validation procedure ( R 2 = 0.54, RMSE = 0.47).