Chemistry:2C-B-3PIP

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2C-B-3PIP, also known as 3-(4-bromo-2,5-dimethoxyphenyl)piperidine, is a serotonin receptor modulator of the phenethylamine, 2C, and 3-phenylpiperidine (3PIP) families related to the psychedelic drug LPH-5 ((S)-2C-TFM-3PIP).[1][2][3][4] It is a cyclized phenethylamine and is the derivative of 2C-B in which the β position has been connected to the amine to form a piperidine ring.[1][2][3][4]

Pharmacology

Pharmacodynamics

The drug is a racemic mixture of (R)- and (S)- enantiomers.[4] The eutomer or (S)- enantiomer is a serotonin 5-HT2A receptor partial agonist with an EC50 of 69 nM and an Emax of 37%, whereas this enantiomer was inactive as an agonist of the serotonin 5-HT2C receptor (EC50 = >50,000 nM) and instead showed low-potency antagonism at this receptor with an IC50 of 640 nM.[4] The distomer or (R)- enantiomer is a serotonin 5-HT2A receptor partial agonist with an EC50 of 370 nM and Emax of 67% as well as a serotonin 5-HT2C receptor partial agonist with an EC50 of 1,900 nM and Emax of 34%.[4] The enantiomers are both dramatically less potent as serotonin 5-HT2A and 5-HT2C receptor agonists than 2C-B, which had an EC50 (Emax) of 1.6 nM (68%) at the serotonin 5-HT2A receptor and an EC50 (Emax) of 4.1 nM (74%) at the serotonin 5-HT2C receptor.[4] 2C-B-3PIP and its enantiomers were not assessed in animal behavioral studies and it is unknown whether they produce psychedelic-type effects.[3][4]

Chemistry

The chemical synthesis of 2C-B-3PIP has been described.[1][2][4] Derivatives of 2C-B-3PIP include the NBOMe-like 2C-B-3PIP-NBOMe and 2C-B-3PIP-POMe.[1][2][5] Some notable analogues of 2C-B-3PIP include 2C-B, LPH-5 ((S)-2C-TFM-3PIP), 2C-B-PYR, ZC-B (2C-B-AZET), 2C-B-morpholine (2C-B-MOR), 2C-B-aminorex (2C-B-AR), 2C-B-PP, and DMBMPP, among others.[4][5][1]

History

2C-B-3PIP was first described in the scientific literature by Martin Hansen in 2010.[1] Its pharmacology was subsequently described by Emil Märcher-Rørsted and colleagues in association with Lophora in the 2020s.[3][4] The closely related drug LPH-5, which is a selective serotonin 5-HT2A receptor agonist and psychedelic drug, is under development by Lophora for the treatment of major depressive disorder.[6][4][7][8][9]

See also

  • Cyclized phenethylamine
  • Substituted 3-phenylpiperidine
  • Partial ergoline

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 Hansen M (2010-12-16). Design and Synthesis of Selective Serotonin Receptor Agonists for Positron Emission Tomography Imaging of the Brain (Ph.D. thesis). University of Copenhagen. doi:10.13140/RG.2.2.33671.14245.
  2. ↑ 2.0 2.1 2.2 2.3 "Extensive rigid analogue design maps the binding conformation of potent N-benzylphenethylamine 5-HT2A serotonin receptor agonist ligands". ACS Chemical Neuroscience 4 (1): 96–109. January 2013. doi:10.1021/cn3000668. PMID 23336049. 
  3. ↑ 3.0 3.1 3.2 3.3 "5-ht2a agonists for use in treatment of depression". 5 November 2020. https://patents.google.com/patent/US20210137908A1/en. 
  4. ↑ 4.00 4.01 4.02 4.03 4.04 4.05 4.06 4.07 4.08 4.09 4.10 "Discovery and Structure-Activity Relationships of 2,5-Dimethoxyphenylpiperidines as Selective Serotonin 5-HT2A Receptor Agonists". Journal of Medicinal Chemistry 67 (9): 7224–7244. May 2024. doi:10.1021/acs.jmedchem.4c00082. PMID 38648420. 
  5. ↑ 5.0 5.1 (in de) Phenethylamine: von der Struktur zur Funktion. Nachtschatten-Science (1 ed.). Solothurn: Nachtschatten-Verlag. 2013. ISBN 978-3-03788-700-4. OCLC 858805226. https://books.google.com/books?id=-Us1kgEACAAJ. Retrieved 19 December 2025. 
  6. ↑ "The Utility of DOI For the Study of Serotonin 2A and 2C Receptors". Molecular Pharmacology. 2025. doi:10.1016/j.molpha.2025.100093. 
  7. ↑ "The Selective Serotonin 5‑HT2A Receptor Agonist (S)‑3-(2,5-Dimethoxy-4-(trifluoromethyl)phenyl)piperidine (LPH-5) Induces Persistent and Robust Antidepressant-Like Effects in Rodents". ACS Pharmacology & Translational Science 8 (6): 1791–1803. June 2025. doi:10.1021/acsptsci.5c00208. PMID 40534669. 
  8. ↑ "LPH 5". 11 November 2025. https://adisinsight.springer.com/drugs/800068514. 
  9. ↑ "Delving into the Latest Updates on LPH-5 with Synapse". 15 November 2025. https://synapse.patsnap.com/drug/82143474e4ab4af6b4499c60d6877e8a. 



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