N -Benzyl-Tryptamine Derivatives as Serotonin 5-HT 2 Receptor Ligands: Synthesis and Structure-Affinity/Activity Relationships
ACS Omega May 13, 2026 Darío Martínez-afani, Breno A. Soares, Jaime Mella-Raipán et al. 1 citation
A set of 22 tryptamine and 22 5-methoxytryptamine derivatives with various N-benzyl substituents were synthesized and tested for affinity and potency at serotonin 5-HT2A, 5-HT2B, and 5-HT2C receptors. The data enabled QSAR analysis, which showed that meta-substitution on the benzyl ring improves activity, while para-substitution reduces it. These effects are attributed to favorable van der Waals interactions at the meta position and steric hindrance at the para position. The findings suggest that N-benzyltryptamines, previously overlooked as psychedelic ligands, could be leads for treating cognitive disorders, substance abuse, or depression.