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Synthesis and Biological Evaluation of 4‑Bromo-N,N-dimethyltryptamine (4-Br-DMT): A Synthetic Building Block for Future Analog Development.

Created on 10 Jul 2026

Authors

Elena Bray, Grant C Glatfelter, Alexander D Maitland, Nicholas R Gonzalez, Donna Walther, Jeanine Yacoub, Michael H Baumann, Jacqueline L von Salm

Published in

ACS omega. Volume 11. Issue 26. Pages 39102-39113. Jul 07, 2026. Epub Jun 23, 2026.

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.

PMID:
42428867
Bibliographic data and abstract were imported from PubMed on 10 Jul 2026.

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