Synthesis and BiologicalEvaluation of 4‑Bromo-N,N-dimethyltryptamine(4-Br-DMT): A Synthetic BuildingBlock for Future Analog Development
Elena Bray, Grant C. Glatfelter, Alexander D. Maitland, Nicholas R. Gonzalez, Donna Walther, Jeanine Yacoub, Michael H. Baumann (8785529), Jacqueline L. von Salm
Figshare June 23, 2026 Peer reviewed DOI: 10.1021/acsomega.6c02996.s001 via OpenAlex
Summary
A synthesis of 4-bromo-N,N-dimethyltryptamine (4-Br-DMT) was achieved, allowing for the creation of new tryptamine analogs to study their effects on serotonergic targets. While 4-Br-DMT exhibits a serotonergic profile, it does not produce psychedelic-like effects in mice and shows a reduced safety profile compared to psilocin and DMT.
Study at a glance
| Population | mice |
|---|---|
| Key finding | 4-Br-DMT has a serotonergic profile without psychedelic-like effects in mice but has a reduced safety profile compared to psilocin and DMT. |
Abstract
The ongoing psychedelic renaissance has prompted a renewed search for novel drugs based on modifying existing psychedelic motifs. In this study, a synthesis of 4-bromo-N,N-dimethyltryptamine (4-Br-DMT) was achieved and used as a late-stage intermediate for analog development. Specifically, we were able to synthesize and access novel molecules by forming carbon–carbon bonds at the C4 position using palladium cross-coupling reactions. Using the synthetic route described here will facilitate the rapid development of a library of tryptamines with novel 4-position substitutions to investigate structure–activity relationships (SARs) with serotonergic targets. Furthermore, the pharmacological target profile and biological effects of 4-Br-DMT were compared to the 4-hydroxy-N,N-dimethyltryptamine (psilocin) and nonring-substituted analog, N,N-dimethyltryptamine (DMT). Overall, the data indicate that 4-Br-DMT has a serotonergic profile without psychedelic-like effects in mice but has a reduced safety profile compared to psilocin and DMT.