Substituted benzofuran

The substituted benzofurans are a class of chemical compounds based on the heterocyclyc and polycyclic compound benzofuran. Many medicines use the benzofuran core as a scaffold,[1][2][3] but most commonly the term is used to refer to the simpler compounds in this class which include numerous psychoactive drugs, including stimulants, psychedelics and empathogens. In general, these compounds have a benzofuran core to which a 2-aminoethyl group is attached (at any position), and combined with a range of other substituents.[4][5][6] Some psychoactive derivatives from this family have been sold under the name Benzofury.[7]

General chemical structure of substituted benzofurans

List of substituted benzofurans

The derivatives may be produced by substitutions at six locations of the benzofuran molecule, as well as saturation of the 2,3- double bond.

The following table displays notable derivatives that have been reported:[8][9][10][11][12][13][14][15][16][17][18]

Structure Compound R2 R3 R4 R5 R6 R7 Other modification
2-APB2-aminopropylHHHHH-
2-MAPB2-(methylamino)propylHHHHH-
2-EAPB2-(ethylamino)propylHHHHH-
BPAP2-(propylamino)pentylHHHHH-
Brofaromine4-piperidinylHHmethoxyHbromo-
3-APBH2-aminopropylHHHH-
DimemebfeH2-(dimethylamino)ethylHmethoxyHH-
MebfapH2-aminopropylHmethoxyHH-
5-MeO-DiBFH2-(diisopropylamino)ethylHmethoxyHH-
4-APBHH2-aminopropylHHH-
DOB-5-HEMIFLY
(5-MeO-7-Br-4-APDB)		HH2-aminopropylmethoxyHbromo2,3-dihydro
5-APBHHH2-aminopropylHH-
5-MAPBHHH2-(methylamino)propylHH-
5-EAPBHHH2-(ethylamino)propylHH-
5-APB-NBOMeHHH2-[(2-methoxybenzyl)amino]propylHH-
6-APBHHHH2-aminopropylH-
6-MAPBHHHH2-(methylamino)propylH-
6-EAPBHHHH2-(ethylamino)propylH-
5-AEDBHHH2-aminoethylHH2,3-dihydro
5-APDBHHH2-aminopropylHH2,3-dihydro
5-MAPDBHHH2-(methylamino)propylHH2,3-dihydro
5-EAPDBHHH2-(ethylamino)propylHH2,3-dihydro
6-APDBHHHH2-aminopropylH2,3-dihydro
6-MAPDBHHHH2-(methylamino)propylH2,3-dihydro
6-EAPDBHHHH2-(ethylamino)propylH2,3-dihydro
bk-5-MAPBHHH1-oxo-2-(methylamino)propylHH-
bk-6-MAPBHHHH1-oxo-2-(methylamino)propylH-
5-MBPBHHH2-(methylamino)butylHH-
6-MBPBHHHH2-(methylamino)butylH-
5-DBFPVHHH1-oxo-2-(pyrrolidin-1-yl)pentylHH2,3-dihydro
6-MeO-5-APDBHHH2-aminopropylmethoxyH2,3-dihydro
F-2methylHHmethoxy2-aminopropylH2,3-dihydro
F-22dimethylHHmethoxy2-aminopropylH2,3-dihydro
7-APBHHHHH2-aminopropyl-
DOI-2-HEMIFLY
(4-I-5-MeO-7-APDB)		HHiodomethoxyH2-aminopropyl2,3-dihydro
2C-B-FLY H H 2-aminoethyl 5,6-dihydrofuro[5,6-f] - bromo 2,3-dihydro
2C-B-DRAGONFLY H H 2-aminoethyl furo[5,6-f] - bromo -
2C-C-FLY H H 2-aminoethyl 5,6-dihydrofuro[5,6-f] - chloro 2,3-dihydro
2C-I-FLY H H 2-aminoethyl 5,6-dihydrofuro[5,6-f] - iodo 2,3-dihydro
2C-D-FLY H H 2-aminoethyl 5,6-dihydrofuro[5,6-f] - methyl 2,3-dihydro
2C-E-FLY H H 2-aminoethyl 5,6-dihydrofuro[5,6-f] - ethyl 2,3-dihydro
2C-EF-FLY H H 2-aminoethyl 5,6-dihydrofuro[5,6-f] - 2-fluoroethyl 2,3-dihydro
2C-T-7-FLY H H 2-aminoethyl 5,6-dihydrofuro[5,6-f] - n-propylthio 2,3-dihydro
DOB-FLY H H 2-aminopropyl 5,6-dihydrofuro[5,6-f] - bromo 2,3-dihydro
Bromo-DragonFLY H H 2-aminopropyl furo[5,6-f] - bromo -
DOB-2-DRAGONFLY
-5-BUTTERFLY		 H H 2-aminopropyl 5,6-dihydropyrano - bromo -
DOM-FLY H H 2-aminopropyl 5,6-dihydrofuro[5,6-f] - methyl 2,3-dihydro
2C-B-FLY-NBOMe H H 2-[(2-methoxybenzyl)amino]ethyl 5,6-dihydrofuro[5,6-f] - bromo 2,3-dihydro
2C-B-DRAGONFLY-NBOH H H 2-[(2-hydroxybenzyl)amino]ethyl furo[5,6-f] - bromo -
TFMFly H H 2-aminopropyl 5,6-dihydrofuro[5,6-f] - trifluoromethyl 2,3-dihydro
Mescaline-FLY H H 2-aminoethyl 5,6-dihydrofuro[5,4-b] - methoxy 2,3-dihydro
YM-348 ethyl H 1-(2-aminopropyl)pyrazol[4,5-f] - H H -
2-desethyl-YM-348 H H 1-(2-aminopropyl)pyrazol[4,5-f] - H H -

Legislation

Substituted benzofurans saw widespread use as recreational drugs by being sold as research chemicals making them exempt from drug legislation. Many of the more common compounds were banned in the UK on June 2013 as temporary class drugs, while others have been made permanently illegal in various jurisdictions.[19][20][21]

See also

References
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  2. Nevagi RJ, Dighe SN, Dighe SN. Biological and medicinal significance of benzofuran. Eur J Med Chem. 2015 Jun 5;97:561-81. doi:10.1016/j.ejmech.2014.10.085
  3. Khanam H, Shamsuzzaman. Bioactive Benzofuran derivatives: A review. Eur J Med Chem. 2015 Jun 5;97:483-504. PMID 25482554 doi:10.1016/j.ejmech.2014.11.039
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  7. Roque Bravo R, Carmo H, Carvalho F, Bastos ML, Dias da Silva D. Benzo fury: A new trend in the drug misuse scene. J Appl Toxicol. 2019 Aug;39(8):1083-1095. doi:10.1002/jat.3774
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  10. US patent 7045545, Karin Briner, Joseph Paul Burkhart, Timothy Paul Burkholder, Matthew Joseph Fisher, William Harlan Gritton, Daniel Timothy Kohlman, Sidney Xi Liang, Shawn Christopher Miller, Jeffrey Thomas Mullaney, Yao-Chang Xu, Yanping Xu, "Aminoalkylbenzofurans as serotonin (5-HT(2c)) agonists", published 19 January 2000, issued 16 May 2006
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  13. Nichols DE, Hoffman AJ, Oberlender RA, Riggs RM. Synthesis and evaluation of 2,3-dihydrobenzofuran analogues of the hallucinogen 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane: drug discrimination studies in rats. J Med Chem. 1986 Feb;29(2):302-4. PMID 3950910
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