Design and Synthesis of Novel 5-ht2a/2c Receptor Agonists Design and Synthesis of Novel 5-ht2a/2c Receptor Agonists

ABSTRACT The neurotransmitter, serotonin (5-hydroxytryptamine, 5-HT), has been linked to such human mental processes as mood sleep and dreaming, sexual behavior, aggression, depression, anxiety, and hallucinogenesis. Serotonin is considered to be relevant in the pathogenesis of several mental and psychosomatic disorders. By understanding the structure of the receptors serotonin binds to, drugs with increased potency and decreased unwanted side effects can be developed. Considering that receptor affinity directly correlates to how closely a ligand’s shape matches that of the receptor-binding site, molecular probes with high affinity for the receptor are commonly used to characterize the receptor’s three-dimensional shape. New drug molecules are currently being synthesized in our own lab at UWLa Crosse for these purposes. The primary focus of this article is to describe the selective methyl-ether cleavage step in the synthesis of two novel, high-affinity 5HT2 receptor probes. This synthetic work will ultimately lead to two 5-HT agonist ligands that will further serve to characterize the receptor. The knowledge gained from this research may improve our understanding of and treatment for the many emotional and behavioral disorders linked to the neurotransmitter, serotonin.