A rationale for the activity profile of arylpiperazinylthioalkyls as 5-HT1A-serotonin and α1-adrenergic receptor ligands

The 5-HT1A and α1-receptor binding affinities of the arylpiperazinylthioalkyl derivatives have been quantitatively expressed in terms of topological and molecular features. The analysis revealed that a lower value of atomic composition based index (AAC), higher values of structural information content (SIC3) and topological charge index (GGI9) would be beneficial to the 5-HT1A receptor binding. For the α1-receptor binding affinity the higher values of topological charge index (GGI9) and atomic Sanderson electronegativities weighted descriptor (GATS3e) and more number of hydrogen atoms attached to sp or sp3 hybridized carbon atoms in a molecular structure (H-047) would be favorable. The derived significant models may further be used to synthesize new potential and selective compounds.

Graphical abstractThe QSAR analysis of the 5-HT1A- and α1-receptor binding affinities and selectivity of the arylpiperazinylthioalkyl derivatives suggest that the substituent groups hold scope for further modification in the optimization of the activity.Figure optionsDownload full-size imageDownload as PowerPoint slide