Synthesis of Selective 5-HT7 Receptor Antagonists

The 5-HT7 receptor is the most recent addition to the 5-HT receptor family and has been linked to a variety of physiological and pathophysiological processes. Well established antidepressant pharmaceuticals have recently been found to activate the 5-HT7 receptor, supporting the role of the 5-HT7 receptor in the antidepressant mechanism. The synthesis of potent selective 5-HT7 receptor antagonists could afford a greater understanding of the 5-HT7 receptor function as well as lead to potential drug candidates. The synthesis of unfused biheteroaryl derivatives as 5-HT7 receptor ligands has been described within. These compounds have been tested for biological activity on the 5-HT6 and 5HT7 receptors. 4-(3’-Furyl)-2-(N-substituted-piperazino)pyrimidines were found to be potent 5HT7 receptor ligands. 4-(2’-Furyl)-2-(N-substituted-piperazino)pyrimidines have shown high selectivity for the 5-HT7 receptor over the 5-HT6 receptor. INDEX WORDS: Serotonin, 5-HT7 receptor, Organic, Heterocyclic chemistry, Synthesis, Pyrimidine, Piperazine, Biheteroaryl SYNTHESIS OF SELECTIVE 5-HT7 RECEPTOR ANTAGONISTS