Cp-mlr Directed Qsar Rationales for the Activity Profile of (phenylpiperazinyl-alkyl) Oxindoles as 5-ht7 Receptor Ligands

The 5-HT7 receptor binding affinities of the oxindole derivatives have been quantitatively analyzed in terms of Dragon descriptors. The derived QSAR models have provided rationales to explain the binding affinity of titled compounds. In order to improve the 5-HT7 receptor binding affinity of a compound higher value of molecular topology and symmetry accounting parameter path/walk 2Randic shape index (descriptor PW2) and lower value of eigenvector coefficient sum from adjacency matrix (descriptor VEA1) are favorable. Presence of more number of sp3 hybridized secondary carbon atoms (descriptor nCs) and secondary aliphatic amides (descriptor nCONHR) in a molecule will be supportive to the activity. The associations of masses to the eigenvalue n.4 of Burden matrix (BEHm4), van der Waals volume to path length 2 of Geary autocorrelation (GATS2v) and Sanderson electronegativity to path length 6 of Moran autocorrelation (MATS6e) and path length 4 of Geary autocorrelation (GATS4e) have shown the prevalence of atomic properties and charge content in terms of 9th and 5th order topological and mean topological charge indices (GGI9 and JGI5) to explain the binding affinity. The PLS analysis has also confirmed the dominance of information content of the CP‐MLR identified descriptors. The derived models and participating descriptors in them have suggested that the substituents of oxindole moiety have sufficient scope for further modification.