DOx

For other uses, see Dox.
2,5-Dimethoxyamphetamine (2,5-DMA), the base structure of the DOx family

4-Substituted-2,5-dimethoxyamphetamines (DOx) is a chemical class of substituted amphetamine derivatives featuring methoxy groups at the 2- and 5- positions of the phenyl ring, and a substituent such as alkyl or halogen at the 4- position of the phenyl ring.[1] Most compounds of this class are potent and long-lasting psychedelic drugs, and act as highly selective 5-HT2A, 5-HT2B, and 5-HT2C receptor partial agonists. A few bulkier derivatives such as DOAM have similarly high binding affinity for 5-HT2 receptors but instead act as antagonists, and so do not produce psychedelic effects though they retain amphetamine-like stimulant effects.

Some of the DOx drugs, including DOB, DOET, DOI, and DOM, are agonists of the rat, rhesus monkey, and/or human TAAR1.[2][3]

DOx derivatives

The DOx family includes the following members:

Structure Name Abbreviation CAS number
2,5-Dimethoxy-4-amylamphetamine DOAM 63779-90-8
2,5-Dimethoxy-4-bromoamphetamine DOB 64638-07-9 (racemate)
2,5-Dimethoxy-4-butylamphetamine DOBU 63779-89-5
2,5-Dimethoxy-4-chloroamphetamine DOC 123431-31-2
2,5-Dimethoxy-4-ethoxyamphetamine MEM 16128-88-4
2,5-Dimethoxy-4-(methoxymethyl)amphetamine DOMOM [4] 260810-10-4
2,5-Dimethoxy-4-(ethoxymethyl)amphetamine DOMOE 930836-81-0
2,5-Dimethoxy-4-ethylamphetamine DOET 22004-32-6
2,5-Dimethoxy-4-ethylthioamphetamine Aleph-2 185562-00-9
2,5-Dimethoxy-4-fluoroamphetamine DOF 125903-69-7
2,5-Dimethoxy-4-(2-fluoroethyl)amphetamine DOEF 121649-01-2
2,5-Dimethoxy-4-(3-fluoropropyl)amphetamine DOPF
2,5-Dimethoxy-4-iodoamphetamine DOI 42203-78-1
2,5-Dimethoxy-4-isopropylthioamphetamine Aleph-4 123643-26-5
2,5-Dimethoxy-4-methylamphetamine DOM 15588-95-1
2,5-Dimethoxy-4-methylthioamphetamine Aleph-1 61638-07-1
2,5-Dimethoxy-4-nitroamphetamine DON 67460-68-8
2,5-Dimethoxy-4-phenylthioamphetamine Aleph-6 952006-44-9
2,5-Dimethoxy-4-benzylamphetamine DOBZ [5] 125903-73-3
2,5-Dimethoxy-4-(3-methoxybenzyl)amphetamine DO3MeOBZ [6] 930836-90-1
2,5-Dimethoxy-4-[(tetrahydrofuran-2-yl)methyl]amphetamine DOTHFM 930776-12-8
2,5-Dimethoxy-4-propylamphetamine DOPR 63779-88-4
2,5-Dimethoxy-4-isopropylamphetamine DOiP 42306-96-7
2,5-Dimethoxy-4-propylthioamphetamine Aleph-7 207740-16-7
2,5-Dimethoxy-4-(difluoromethyl)amphetamine DODFM
2,5-Dimethoxy-4-trifluoromethylamphetamine DOTFM 159277-07-3
2,5-Dimethoxy-4-(2,2,2-trifluoroethyl)amphetamine DOTFE [7]
2,5-Dimethoxy-4-cyanoamphetamine DOCN [8] 125903-74-4
2,5-Dimethoxy-4-ethynylamphetamine DOYN [9] 633290-70-7

A number of additional compounds are known with alternative substitutions:

Structure Name Abbreviation CAS number
Dimoxamine ("Ariadne") 4C-D 52842-59-8
1-(2,5-Dimethoxy-4-ethylphenyl)butan-2-amine [10] 4C-E
1-(2,5-Dimethoxy-4-(n-propyl)phenyl)butan-2-amine 4C-P
1-(2,5-Dimethoxy-4-bromophenyl)butan-2-amine 4C-B 69294-23-1
1-(2,5-Dimethoxy-4-chlorophenyl)butan-2-amine 4C-C 791010-74-7
1-(2,5-Dimethoxy-4-iodophenyl)butan-2-amine 4C-I 758631-75-3
1-(2,5-Dimethoxy-4-nitrophenyl)butan-2-amine 4C-N 775234-58-7
1-[2,5-Dimethoxy-4-(ethylthio)phenyl]butan-2-amine 4C-T-2 850007-13-5
Dimethoxymethamphetamine ("Beatrice") N-methyl-DOM 92206-37-6
2,5-Dimethoxy-3,4-methylenedioxyamphetamine DMMDA 15183-13-8
2,5-dimethoxy-3,4-dimethylamphetamine ("Ganesha") 3-methyl-DOM 207740-37-2
2,5-Dimethoxy-3,4-trimethylenylamphetamine G-3
2,5-Dimethoxy-3,4-tetramethylenylamphetamine G-4
2,5-Dimethoxy-3,4-norbornylamphetamine G-5
1-(5,8-dimethoxy-3,4-dihydro-1H-isochromen-7-yl)propan-2-amine [11] G-O 774538-38-4
2,5-Dimethoxy-3,4-dichloroamphetamine DODC 1373918-65-0
IDNNA IDNNA 67707-78-2
Methyl-DOB N-methyl-DOB 155638-80-5
2,3,4,5-Tetramethoxyamphetamine 2,3,4,5-Tetramethoxyamphetamine 23693-26-7
1-(4-Bromo-2,3,6,7-tetrahydrofuro[2,3-f][1]benzofuran-8-yl)propan-2-amine DOB-FLY 219986-75-1
Bromo-DragonFLY DOB-DFLY 502759-67-3
3-(4-bromo-2,5-dimethoxyphenyl)azetidine Compound 1,[12] ZC-B

See also

References

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  2. ^ Lewin AH, Miller GM, Gilmour B (December 2011). "Trace amine-associated receptor 1 is a stereoselective binding site for compounds in the amphetamine class". Bioorg Med Chem. 19 (23): 7044–7048. doi:10.1016/j.bmc.2011.10.007. PMC 3236098. PMID 22037049.
  3. ^ Bunzow JR, Sonders MS, Arttamangkul S, Harrison LM, Zhang G, Quigley DI, Darland T, Suchland KL, Pasumamula S, Kennedy JL, Olson SB, Magenis RE, Amara SG, Grandy DK (December 2001). "Amphetamine, 3,4-methylenedioxymethamphetamine, lysergic acid diethylamide, and metabolites of the catecholamine neurotransmitters are agonists of a rat trace amine receptor". Mol Pharmacol. 60 (6): 1181–1188. doi:10.1124/mol.60.6.1181. PMID 11723224.
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  5. ^ Nelson DL, Lucaites VL, Wainscott DB, Glennon RA. Comparisons of hallucinogenic phenylisopropylamine binding affinities at cloned human 5-HT2A, 5-HT2B and 5-HT2C receptors. N-S. Arch. Pharmacol., 1 Jan 1999, 359(1): 1–6. doi:10.1007/PL00005315
  6. ^ Hellberg M, Namil A, Feng Z, Ward J. Phenylethylamine Analogs and Their Use for Treating Glaucoma. Patent WO 2007/038372, 6 Apr 2007
  7. ^ Trachsel D. Fluorine in psychedelic phenethylamines. Drug Test. Anal., 1 Jul 2012, 4(7-8): 577-590.doi:10.1002/dta.413
  8. ^ Seggel MR, Yousif MY, Lyon RA, Titeler M, Roth BL, Suba EA, Glennon, RA. A structure-affinity study of the binding of 4-substituted analogues of 1-(2,5-dimethoxyphenyl)-2-aminopropane at 5-HT2 serotonin receptors. J. Med. Chem., 1 Mar 1990, 33(3): 1032–1036. doi:10.1021/jm00165a023
  9. ^ Trachsel D (August 2003). "Synthesis of Novel (Phenylalkyl) amines for the Investigation of Structure–Activity Relationships, Part 3: 4-Ethynyl-2,5-dimethoxyphenethylamine (= 4-Ethynyl-2, 5-dimethoxybenzeneethanamine; 2C-YN)". Helvetica Chimica Acta. 86 (8): 2754–9. doi:10.1002/hlca.200390224.
  10. ^ Shulgin AT. Treatment of senile geriatric patients to restore performance. Patent US 4034113
  11. ^ Hellberg MR, Namil A. Benzopyran analogs and their use for the treatment of glaucoma. Patent US 7396856
  12. ^ Kristensen J, et al. 5-HT2A Agonists for Use in Treatment of Depression. Patent US 2021/0137908