Search for: [Abstract = "The PhD thesis focuses on structural factors determining selectivity of arylpiperazine and arylsulfonamide derivatives for 5\-HTlA and 5\-HT7 receptors. The synthesis and SAR analysis of pyrrolidine and benzotriazole derivatives confirmed that linearly extended conformation of LCAP is bioactive for 5\-HTlA receptors, whereas this geometry is unfavorable for the 5\-HT7 receptors. In the group of benzisoxazolepiperazine derivatives the use of sulfonamide fragment, additionally rigidified by the piperidine ring, is significant for high affinity for 5\-HT7R\; however, the activity toward 5\-HT1AR \(and others monoaminergic receptors\) is not completely eliminated. It was found, that the lack of aromatic groups m the vicinity of protonated nitrogen atom \(perhydroisoquinoline derivatives\) is essential for selectivity to 5\-HT7R vs 5\-HT1AR. Docking studies showed that these ligands are located between helices 3, 6 and 7, within the so\-called selective part of 5\-HT7R binding pocket. Moreover, based on new arylsulfonamide derivatives the 3D QSAR pharmacophore model was generated. It extends the previous selectivity hypothesis \(obtained in structure\-based approach\), by defining the additional hydrophobic region, located near aromatic feature."]
