Synthesis and Preliminary Screening of Novel Tryptamines as 5-HT4 Receptor Ligands

For the development of novel 5-HT4 receptor ligands we have designed and synthesized two series of 5- methoxytryptamine derivatives varying the substitution on the primary amine. Their biological activities were evaluated in a receptor binding assay where a subset of compounds showed comparable potency to the agonists serotonin and 5- methoxytryptamine. Structure-activity analyses have highlighted promising avenues for further synthetic work and binding modes were proposed by docking these compounds into a homology model of the 5-HT4 receptor. Keywords: 5-HT4 ligands, serotonin, tryptamine, 5-HT4 receptor, medicinal chemistry