Synthesis of ligands for receptors involved in neurodegeneration

My PhD research period focuses on the synthesis of ligands for receptors implicated in neurodegeneration, developed in three main scenarios. In the first case, we aim at producing new selective and potent ligands for well-characterized receptors implicated in neuroprotection, for example the adenosine receptor family. The biochemical rationale through which these receptors mediate neuroprotection has been widely studied in various animal models. Besides, the fact that various ligands for these receptors are promising candidates in clinical trials for the treatment of neurodegenerative disease encourages research proposals in this direction. The second scenario involves a newly deorphanized receptor, GPR17, which has notable functions in the brain. It works as a ''sensor'' of brain damage and its modulation activates cells responsible for remyelination. The design and synthesis of GPR17 ligands will definitely help uncover the therapeutic potential of this receptor in brain injury and demyelinating disorders. The last case involves the design and synthesis of molecules for orphan or not fully characterized receptors. This is the case of the guanosine putative receptor described in Chapter 2. These ligands could be helpful in delineating the physiopathological roles of these receptors, thereby creating new possibilities of pharmacological intervention in various diseases.