Abstract:
The serotonin 5-HT6 binding affinity of indolyl- and piperidinyl-sulfonamide derivatives has been analyzed with the topological and molecular features from Dragon software. Analysis of the structural features in conjunction with the biological endpoints in Combinatorial Protocol in Multiple Linear Regression (CP-MLR) led to the identification of 25 descriptors for modeling the activity. The study clearly suggested the role of average Randic-type eigenvector-based index from adjacency matrix, VRA2, number of secondary aliphatic amines, nNHR, sum of topological distance between N and O, T(N..O), ring tertiary carbon atoms, nCrHR, and CH2RX type fragment, C-006, in a molecular structure to optimize the 5-HT6 binding affinities of titled compounds. The PLS analysis has confirmed the dominance of information content of CP-MLR identified descriptors for modeling the activity when compared to those of leftover ones.
