Structure-activity relationship of newly synthesized biological active compound

The subject of research project is the synthesis, pharmacological and theoretical investigation of the compounds acting upon the certain CNS receptor types. A three-pronged approach to the research has been planned. First part represents the synthesis and characterization of the compounds anticipated to be the active ligands. This includes potential dopaminergic-serotonergic ligands with an atypical antipsyhotic action, or alternatively the compounds acting as D2 dopamine receptor agonists. Other class of synthesized compounds is expected to be potent opioid-receptor ligands, particularly NOP receptor antagonists. Additionally, the development and/or optimization of the ligand precursor syntheses have also been envisaged. Pharmacological aspect of the project includes estimation of the various ligand binding affinities, determination of the ligand properties (i.e. agonist, antagonist, possible neuroprotective action etc.), as well as the animal in vivo experiments. Finally, the theoretical studies will encompass QSAR analysis, molecular dinamics, semiempirical and ab initio calculations as well as the docking analysis of the ligand-receptor interactions. Also, a database containing numereous dopamine and serotonine ligands of the arylpiperazine structure will be formed. The outcome of this combined approach is expected to produce novel ligands with improved overall pharmacological profile. As results of this project it is expect 12 original scientific papers and 3 PhD theses.