Topochemical models for the prediction of permeability through blood–brain barrier

Relationship between the topochemical indices and permeability of diverse series of compounds through blood–brain barrier has been investigated. Three-topochemical indices, Wiener's topochemical index—a distance-based topochemical descriptor, molecular connectivity topochemical index—an adjacency based topochemical descriptor and eccentric connectivity topochemical index—an adjacency-cum-distance based topochemical descriptor, were used for the present investigation. A data set comprising of 28 compounds with established CNS permeation tendency was selected for present study. The values of all the three-topochemical indices in the original as well as in the normalized form for each of the 28 compounds comprising the data set were computed using an in-house computer program. Resultant data was analyzed and suitable models were developed after identification of the permeable ranges. Subsequently, permeability characteristic was assigned to each compound involved in the data set using these models, which was then compared with the reported permeability through blood–brain barrier. Accuracy of prediction was found to vary from a minimum of 83% to a maximum of ∼95% using these models.