EPPTB

Chemical compound

EPPTB
Identifiers

IUPAC name N-(3-ethoxyphenyl)-4-pyrrolidin-1-yl-3-trifluoromethylbenzamide
PubChem CID	25175634
ChemSpider	26387935
Chemical and physical data
Formula	C₂₀H₂₁F₃N₂O₂
Molar mass	378.395 g·mol⁻¹
3D model (JSmol)	Interactive image Interactive image
SMILES CCOc2cc(ccc2)NC(=O)c(cc1C(F)(F)F)ccc1N3CCCC3 CCOc1cccc(c1)NC(=O)c2ccc(c(c2)C(F)(F)F)N3CCCC3
InChI InChI=1S/C20H21F3N2O2/c1-2-27-16-7-5-6-15(13-16)24-19(26)14-8-9-18(25-10-3-4-11-25)17(12-14)20(21,22)23/h5-9,12-13H,2-4,10-11H2,1H3,(H,24,26) Key:KLFVWQCQUXXLOU-UHFFFAOYSA-N

EPPTB (RO-5212773) is a drug developed by Hoffmann-La Roche which acts as a potent and selective inverse agonist of trace amine-associated receptor 1 (TAAR1), with no significant activity at other targets. EPPTB is one of the first selective antagonists developed for TAAR1, and has been used to demonstrate an important role for TAAR1 in regulation of dopaminergic signalling in the limbic system.^[1] Although EPPTB has high affinity for the mouse TAAR1, it has much lower affinity for rat and human TAAR1, which limits its use in research.^[2] While the human and mouse forms of TAAR1 have similar functions and bind similar ligands, the actual binding affinities of individual ligands often vary significantly between the two versions of the receptor.^[3]

References

^ Bradaia A, Trube G, Stalder H, Norcross RD, Ozmen L, Wettstein JG, et al. (November 2009). "The selective antagonist EPPTB reveals TAAR1-mediated regulatory mechanisms in dopaminergic neurons of the mesolimbic system". Proceedings of the National Academy of Sciences of the United States of America. 106 (47): 20081–6. Bibcode:2009PNAS..10620081B. doi:10.1073/pnas.0906522106. PMC 2785295. PMID 19892733.
^ Stalder H, Hoener MC, Norcross RD (February 2011). "Selective antagonists of mouse trace amine-associated receptor 1 (mTAAR1): discovery of EPPTB (RO5212773)". Bioorganic & Medicinal Chemistry Letters. 21 (4): 1227–31. doi:10.1016/j.bmcl.2010.12.075. PMID 21237643.
^ Hu LA, Zhou T, Ahn J, Wang S, Zhou J, Hu Y, Liu Q (October 2009). "Human and mouse trace amine-associated receptor 1 have distinct pharmacology towards endogenous monoamines and imidazoline receptor ligands". The Biochemical Journal. 424 (1): 39–45. doi:10.1042/BJ20090998. PMID 19725810. S2CID 21498991.

Human trace amine-associated receptor ligands

TAAR1

Agonists

Endogenous^†	Classical monoamine neurotransmitters Dopamine Histamine Norepinephrine Serotonin Trace amines 3-Iodothyronamine 3-Methoxytyramine N-Methylphenethylamine N-Methyltyramine m-Octopamine p-Octopamine Phenethylamine Phenylethanolamine Synephrine Tryptamine m-Tyramine p-Tyramine
Synthetic^‡	Amphetamine DOB DOET 4-Hydroxyamphetamine Isoprenaline MDA (tenamfetamine) MDMA (midomafetamine) 2-Methylphenethylamine 3-Methylphenethylamine 4-Methylphenethylamine β-Methylphenethylamine Methamphetamine 3-MMA Norfenfluramine Phentermine o-PIT Propylhexedrine Ralmitaront (RG-7906, RO-6889450) RO5166017 N,N-Dimethylphenethylamine Ulotaront (SEP-363856)

Neutral antagonists

Inverse agonists

EPPTB (RO5212773)

TAAR2

Agonists^‡
Neutral antagonists

TAAR5

Agonists^‡	N,N-Dimethylethylamine Trimethylamine
Neutral antagonists
Inverse agonists^‡	3-Iodothyronamine

^† References for all endogenous human TAAR1 ligands are provided at List of trace amines

^‡ References for synthetic TAAR1 agonists can be found at TAAR1 or in the associated compound articles. For TAAR2 and TAAR5 agonists and inverse agonists, see TAAR for references.

See also: Receptor/signaling modulators