Search for: [Abstract = "The subject of the doctoral dissertation was the discovery of a new generation of functionally selective 5\-HT1A serotonin receptor agonists, of significant importance in the search for the therapy of psychiatric and neurodegenerative disorders. Designed with the support of molecular modeling, a library of 65 new 1\- \(1\-benzoylpiperidin\-4\-yl\) methanamine derivatives was synthesized by chemical synthesis, of which as many as 48 had subnanomolar affinity, and one of the compounds was characterized by the highest affinity of all the 5 HT1AR ligands described so far \(Ki = 0.00016 nM\). Seventeen new 5\-HT1A receptor agonists with different functional activity profiles were identified, including compounds strongly favoring ERK1 \/ 2 phosphorylation or β\-arrestin recruitment, with very high bias factors \(> 1000x\). The new series was characterized by high selectivity for the adrenergic α1 and dopaminergic D2 receptors as well as high values of parameters predicting the drug\-like and developability properties of the tested compounds \(CNS MPO, Fsp3 or LELP\).For the lead structure, high selectivity against 44 off\-targets, high metabolic stability and favorable ADME parameters have been demonstrated. In rat studies it showed striking and dose\-dependent antidepressant activity, observed from very low doses after oral administration \(MED = 0.16 mg\/kg\), achieving an exceptionally high effect size \(total reduction of immobility in the Porsolt test\).All the obtained compounds are the subject of international patent application WO2017220799."]

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