Synthesis Of Chemical Probes And Ligands For Exploratory Studies Involving The Roles Of Ghrelin and Serotonin Receptors In Various Central Nervous System Pathways

Divided into two sections, this dissertation used synthetic chemistry to help understand the role/s of ghrelin and its receptor in substance use disorder, and to explore several ligands to potentially treat mental health disorders by targeting the serotonin 2A receptor. The first section tackles substance use disorder which is now considered a psychiatric disorder that needs to be addressed and treated. Although the mechanism of the disorder is not fully understood and elucidated, there has been growing evidence of the participation of ghrelin and its receptor in the mechanism of substance use disorder. Published data also shows that the ghrelin receptor interacts with the serotonin 2C receptor and unpublished data shows that there is a saturable interaction between the two receptors that potentially participates in the mechanism of substance abuse. Presented here is the synthesis of MK-677 analogues which can be used as a building block to synthesize chemical probes to help understand the role of the interaction of the ghrelin receptor and serotonin 2C receptor in substance use disorder. The second section aims to contribute to the growing treatment for mental health disorders by targeting the serotonin 2A receptor. Research shows that several ligand-receptor interactions such as agonism, inverse agonism, antagonism, and allosteric modulation of the serotonin 2A receptor have benefits in addressing mental health disorders. However, due to varied patients’ response to existing treatments, there is still a need to discover new ligands to treat this problem. In this work, several ligands were synthesized which will be assessed for their affinity and potential ligand-receptor activity towards the serotonin 2A receptor.