Model structure–activity relationship studies of potential tropane 5HT(1A), 5HT(2A), and D(2) receptor ligands

The two-stages studies of structure–activity relationship for model ligands of 5HT(1A), 5HT(2A), and D(2) receptors were performed. On the first stage, the pharmacophores of two potential ligands of known in vitro binding to 5HT(1A), 5HT(2A), D(2) receptors and model pharmacophore of strongly interacting D(2) receptor ligands were found and their parameters were related to affinity data. The analyzed parameters were hydrophobic, hydrophilic, aromatic, donor and acceptor of proton centers. The geometry of spatial distribution of these properties was also investigated in comparative analysis. The studied, model compounds were two 3β-acylamine derivatives of tropane. The second stage includes docking of studied compounds to D(2) receptor model and the comparison of its quality with in vivo binding data. The obtained results are consistent with in vitro binding data and applied procedure accurate estimates the affinity of potential ligands to D(2) receptors.