Substituted benzofuran

General chemical structure of substituted benzofurans

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][7] Some psychoactive derivatives from this family have been sold under the name Benzofury.[8]

List of substituted benzofurans

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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:[9][10][11][12][13][14][15][16][17][18][19]

Structure Compound CAS number R2 R3 R4 R5 R6 R7 Other modification
2-APB 30455-73-3 2-aminopropyl H H H H H -
2-MAPB 806596-15-6 2-(methylamino)propyl H H H H H -
2-EAPB 2-(ethylamino)propyl H H H H H -
BPAP 260550-89-8 2-(propylamino)pentyl H H H H H -
Brofaromine 63638-91-5 4-piperidinyl H H methoxy H bromo -
3-APB 105909-13-5 H 2-aminopropyl H H H H -
Dimemebfe 140853-58-3 H 2-(dimethylamino)ethyl H methoxy H H -
Mebfap 140853-59-4 H 2-aminopropyl H methoxy H H -
5-MeO-DiBF H 2-(diisopropylamino)ethyl H methoxy H H -
4-APB 286834-82-0 H H 2-aminopropyl H H H -
DOB-5-HEMIFLY
(5-MeO-7-Br-4-APDB)		 H H 2-aminopropyl methoxy H bromo 2,3-dihydro
5-APB 286834-81-9 H H H 2-aminopropyl H H -
5-MAPB 1354631-77-8 H H H 2-(methylamino)propyl H H -
5-EAPB 1445566-01-7 H H H 2-(ethylamino)propyl H H -
5-APB-NBOMe H H H 2-[(2-methoxybenzyl)amino]propyl H H -
6-APB 286834-85-3 H H H H 2-aminopropyl H -
6-MAPB 1354631-79-0 H H H H 2-(methylamino)propyl H -
6-EAPB 1632539-47-9 H H H H 2-(ethylamino)propyl H -
5-AEDB H H H 2-aminoethyl H H 2,3-dihydro
5-APDB 152624-03-8 H H H 2-aminopropyl H H 2,3-dihydro
5-MAPDB 1354631-78-9 H H H 2-(methylamino)propyl H H 2,3-dihydro
5-EAPDB H H H 2-(ethylamino)propyl H H 2,3-dihydro
6-APDB 1354631-78-9 H H H H 2-aminopropyl H 2,3-dihydro
6-MAPDB 1354631-81-4 H H H H 2-(methylamino)propyl H 2,3-dihydro
6-EAPDB H H H H 2-(ethylamino)propyl H 2,3-dihydro
bk-5-MAPB H H H 1-oxo-2-(methylamino)propyl H H -
bk-6-MAPB H H H H 1-oxo-2-(methylamino)propyl H -
5-MBPB H H H 2-(methylamino)butyl H H -
6-MBPB H H H H 2-(methylamino)butyl H -
5-DBFPV 2117405-32-8 H H H 1-oxo-2-(pyrrolidin-1-yl)pentyl H H 2,3-dihydro
6-MeO-5-APDB H H H 2-aminopropyl methoxy H 2,3-dihydro
F-2 99355-74-5 methyl H H methoxy 2-aminopropyl H 2,3-dihydro
F-22 952016-51-2 dimethyl H H methoxy 2-aminopropyl H 2,3-dihydro
7-APB 286834-86-4 H H H H H 2-aminopropyl -
DOI-2-HEMIFLY
(4-I-5-MeO-7-APDB)		 H H iodo methoxy H 2-aminopropyl 2,3-dihydro
The chemical structure of amiodarone, a class III antiarrhythmic drug. Amiodarone 1951-25-3 propyl 3,5-diiodo-4-(2-diethylaminoethoxy)benzoyl H H H H -
2C-B-FLY 733720-95-1 H H 2-aminoethyl 5,6-dihydrofuro[5,6-f] - bromo 2,3-dihydro
2C-B-DRAGONFLY 260809-98-1 H H 2-aminoethyl furo[5,6-f] - bromo -
2C-C-FLY 1354633-83-2 H H 2-aminoethyl 5,6-dihydrofuro[5,6-f] - chloro 2,3-dihydro
2C-I-FLY 1354633-88-7 H H 2-aminoethyl 5,6-dihydrofuro[5,6-f] - iodo 2,3-dihydro
2C-D-FLY 1354634-07-3 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 1354633-05-8 H H 2-aminoethyl 5,6-dihydrofuro[5,6-f] - n-propylthio 2,3-dihydro
DOB-FLY 219986-75-1 H H 2-aminopropyl 5,6-dihydrofuro[5,6-f] - bromo 2,3-dihydro
Bromo-DragonFLY 502759-67-3 H H 2-aminopropyl furo[5,6-f] - bromo -
DOB-2-DRAGONFLY-5-BUTTERFLY 1043541-82-7 H H 2-aminopropyl 5,6-dihydropyrano - bromo -
DOM-FLY 748748-08-5 H H 2-aminopropyl 5,6-dihydrofuro[5,6-f] - methyl 2,3-dihydro
DOMOM-FLY [20] H H 2-aminopropyl 5,6-dihydrofuro[5,6-f] - methoxymethyl 2,3-dihydro
2C-B-FLY-NBOMe 1335331-42-4 H H 2-[(2-methoxybenzyl)amino]ethyl 5,6-dihydrofuro[5,6-f] - bromo 2,3-dihydro
2C-B-DRAGONFLY-NBOH 1335331-45-7 H H 2-[(2-hydroxybenzyl)amino]ethyl furo[5,6-f] - bromo -
TFMFly 780744-19-6 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 372163-84-3 ethyl H 1-(2-aminopropyl)pyrazol[4,5-f] - H H -
2-desethyl-YM-348 748116-94-1 H H 1-(2-aminopropyl)pyrazol[4,5-f] - H H -

Legislation

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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 in June 2013 as temporary class drugs, while others have been made permanently illegal in various jurisdictions.[21][22][23]

See also

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References

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  2. ^ Nevagi RJ, Dighe SN, Dighe SN (June 2015). "Biological and medicinal significance of benzofuran". European Journal of Medicinal Chemistry. 97: 561–81. doi:10.1016/j.ejmech.2014.10.085. PMID 26015069.
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  8. ^ Roque Bravo R, Carmo H, Carvalho F, Bastos ML, Dias da Silva D (August 2019). "Benzo fury: A new trend in the drug misuse scene". Journal of Applied Toxicology. 39 (8): 1083–1095. doi:10.1002/jat.3774. PMID 30723925. S2CID 73433890.
  9. ^ Tomaszewski Z, Johnson MP, Huang X, Nichols DE (May 1992). "Benzofuran bioisosteres of hallucinogenic tryptamines". Journal of Medicinal Chemistry. 35 (11): 2061–4. doi:10.1021/jm00089a017. PMID 1534585.
  10. ^ Monte AP, Marona-Lewicka D, Cozzi NV, Nichols DE (November 1993). "Synthesis and pharmacological examination of benzofuran, indan, and tetralin analogues of 3,4-(methylenedioxy)amphetamine". Journal of Medicinal Chemistry. 36 (23): 3700–6. doi:10.1021/jm00075a027. PMID 8246240.
  11. ^ 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 
  12. ^ "Temporary class drug order report on 5-6APB and NBOMe compounds". UK Home Office. 4 June 2013. Retrieved 23 August 2016.
  13. ^ Stanczuk A, Morris N, Gardner EA, Kavanagh P (April 2013). "Identification of (2-aminopropyl)benzofuran (APB) phenyl ring positional isomers in internet purchased products". Drug Testing and Analysis. 5 (4): 270–6. doi:10.1002/dta.1451. PMID 23349125.
  14. ^ Nichols DE, Hoffman AJ, Oberlender RA, Riggs RM (February 1986). "Synthesis and evaluation of 2,3-dihydrobenzofuran analogues of the hallucinogen 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane: drug discrimination studies in rats". Journal of Medicinal Chemistry. 29 (2): 302–4. doi:10.1021/jm00152a022. PMID 3950910.
  15. ^ Nichols DE, Snyder SE, Oberlender R, Johnson MP, Huang XM (January 1991). "2,3-Dihydrobenzofuran analogues of hallucinogenic phenethylamines". Journal of Medicinal Chemistry. 34 (1): 276–81. doi:10.1021/jm00105a043. PMID 1992127.
  16. ^ Monte AP, Marona-Lewicka D, Parker MA, Wainscott DB, Nelson DL, Nichols DE (July 1996). "Dihydrobenzofuran analogues of hallucinogens. 3. Models of 4-substituted (2,5-dimethoxyphenyl)alkylamine derivatives with rigidified methoxy groups". Journal of Medicinal Chemistry. 39 (15): 2953–61. doi:10.1021/jm960199j. PMID 8709129.
  17. ^ Liu C, Jia W, Qian Z, Li T, Hua Z (February 2017). "Identification of five substituted phenethylamine derivatives 5-MAPDB, 5-AEDB, MDMA methylene homolog, 6-Br-MDMA, and 5-APB-NBOMe". Drug Testing and Analysis. 9 (2): 199–207. doi:10.1002/dta.1955. PMID 26856255.
  18. ^ Wagmann L, Brandt SD, Stratford A, Maurer HH, Meyer MR (February 2019). "Interactions of phenethylamine-derived psychoactive substances of the 2C-series with human monoamine oxidases" (PDF). Drug Testing and Analysis. 11 (2): 318–324. doi:10.1002/dta.2494. PMID 30188017. S2CID 52166076.
  19. ^ Wagmann L, Hempel N, Richter LH, Brandt SD, Stratford A, Meyer MR (October 2019). "Phenethylamine-derived new psychoactive substances 2C-E-FLY, 2C-EF-FLY, and 2C-T-7-FLY: Investigations on their metabolic fate including isoenzyme activities and their toxicological detectability in urine screenings". Drug Testing and Analysis. 11 (10): 1507–1521. doi:10.1002/dta.2675. PMID 31299701.
  20. ^ Feng Z, Mohapatra S, Klimko PG, Hellberg MR, May JA, Kelly C, Williams G, McLaughlin MA, Sharif NA. Novel benzodifuran analogs as potent 5-HT2A receptor agonists with ocular hypotensive activity. Bioorg Med Chem Lett. 2007 Jun 1;17(11):2998-3002. doi:10.1016/j.bmcl.2007.03.073 PMID 17419053
  21. ^ UK Home Office (5 March 2014). "The Misuse of Drugs Act 1971 (Ketamine etc.) (Amendment) Order 2014". UK Government. Retrieved 23 August 2016.
  22. ^ "关于印发《非药用类麻醉药品和精神药品列管办法》的通知" (in Chinese). China Food and Drug Administration. 27 September 2015. Archived from the original on 1 October 2015. Retrieved 23 August 2016.
  23. ^ "指定薬物名称・構造式一覧（平成27年9月16日現在）" (PDF) (in Japanese). 厚生労働省. 16 September 2015. Retrieved 23 August 2016.
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