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List of fentanyl analogues

This is a list of fentanyl analogues, including both compounds developed by pharmaceutical companies for legitimate medical use, and those which have been sold as designer drugs and reported to national drug control agencies such as the DEA, or transnational agencies such as the EMCDDA and UNODC.[1][2][3][4][5] This is not a comprehensive listing of fentanyl analogues, as more than 1400 compounds from this family have been described in the scientific and patent literature,[6][7] but it includes all notable compounds that have reached late-stage human clinical trials, or which have been identified as having been sold as designer drugs.

In the United States, the Drug Enforcement Agency placed the broadly defined class of "Fentanyl-Related Substances" on the list of Schedule I drugs in 2018, making it illegal to manufacture, distribute, or possess fentanyl analogs.[8]

Chemical structures of various fentanyl analogues

Chemical structure Common name Chemical name CAS number
Phenaridine.svg 2,5-Dimethylfentanyl N-[2,5-Dimethyl-1-(2-phenylethyl)piperidin-4-yl]-N-phenylpropanamide 42045-97-6
2,2'-Difluorofentanyl structure.png 2,2'-Difluorofentanyl N-(2-Fluorophenyl)-N-[1-(2-[2-fluorophenyl]ethyl)-4-piperidinyl]-propanamide
3-allylfentanyl.svg 3-Allylfentanyl N-[(3S,4R)-1-Phenethyl-3-prop-2-enylpiperidin-4-yl]-N-phenylpropanamide 82208-84-2
Nfepp.png 3-Fluorofentanyl (NFEPP) N-(3-Fluoro-1-phenethylpiperidin-4-yl)-N-phenylpropionamide 1422952-84-8
3-Furanylfentanyl structure.png 3-Furanylfentanyl (3FUF) N-Phenyl-N-[1-(2-phenylethyl)piperidin-4-yl]furan-3-carboxamide 101343-82-2
3-Methylbutyrfentanyl structure.png 3-Methylbutyrfentanyl N-[3-Methyl-1-(2-phenylethyl)piperidin-4-yl]-N-phenylbutanamide 97605-09-9
3-Methylfentanyl.svg 3-Methylfentanyl (3-MF) N-(3-methyl-1-phenethyl-4-piperidyl)-N-phenyl-propanamide 42045-86-3
3-Methylfuranylfentanyl structure.png 3-Methylfuranylfentanyl[9] (3MFUF, TMFUF) N-Phenyl-N-[3-methyl-1-(2-phenylethyl)piperidin-4-yl]furan-2-carboxamide
3-Methylthiofentanyl.svg 3-Methylthiofentanyl N-{3-Methyl-1-[2-(2-thienyl)ethyl]piperidin-4-yl}-N-phenylpropanamide 86052-04-2
3-Phenylpropanoylfentanyl structure.png 3-Phenylpropanoylfentanyl N-Phenyl-N-[1-(2-phenylethyl)piperidin-4-yl]-3-phenylpropanamide 79279-02-0
4-Fluorobutyrfentanyl.png 4-Fluorobutyrfentanyl (4-FBF) N-(4-Fluorophenyl)-N-[1-(2-phenylethyl)-4-piperidinyl]-butanamide 244195-31-1
PCl-IBF structure.png 4-Chloroisobutyrylfentanyl (4-CIBF) 2-Methyl-N-(4-chlorophenyl)-N-[1-(1-phenylpropan-2-yl)piperidin-4-yl]propanamide 244195-34-4
4-Fluoroisobutyrfentanyl.svg 4-Fluoroisobutyrfentanyl (4-FIBF) N-(4-Fluorophenyl)-N-[1-(2-phenylethyl)-4-piperidinyl]-isobutanamide 244195-32-2
Parafluorofentanyl.svg 4-Fluorofentanyl N-(4-fluorophenyl)-N-[1-(2-phenylethyl)piperidin-4-yl]propanamide 90736-23-5
Parafluorofuranylfentanyl structure.png para-fluorofuranylfentanyl (p-F-Fu-F) N-(1-phenethylpiperidin-4-yl)-N-(4-fluorophenyl)furan-2-carboxamide 1802489-71-9
Parachlorofuranylfentanyl structure.png para-chlorofuranylfentanyl (p-Cl-Fu-F) N-(1-phenethylpiperidin-4-yl)-N-(4-chlorophenyl)furan-2-carboxamide
Orthomethylfuranylfentanyl structure.png ortho-methylfuranylfentanyl (o-Me-Fu-F) N-(1-phenethylpiperidin-4-yl)-N-(o-tolyl)furan-2-carboxamide
Orthomethoxyfuranylfentanyl structure.png ortho-methoxyfuranylfentanyl (o-MeO-Fu-F) N-(1-phenethylpiperidin-4-yl)-N-(2-methoxyphenyl)furan-2-carboxamide
Orthoisopropylfuranylfentanyl structure.png ortho-isopropylfuranylfentanyl (o-iPr-Fu-F) N-(1-phenethylpiperidin-4-yl)-N-(2-isopropylphenyl)furan-2-carboxamide
4-Phenylfentanyl.png 4-Phenylfentanyl N-Phenyl-N-[4-phenyl-1-(2-phenylethyl)piperidin-4-yl]propanamide 120448-97-7
4-Methoxybutyrfentanyl.svg 4-Methoxybutyrfentanyl N-(4-Methoxyphenyl)-N-[1-(2-phenylethyl)-4-piperidinyl]-butanamide 2088842-68-4
4-Methylphenethylacetylfentanyl structure.png 4-Methylphenethylacetylfentanyl N-[1-[2-(4-Methylphenyl)ethyl]-4-piperidinyl]-N-phenylacetamide 1071703-95-1
Acrylfentanyl.svg Acrylfentanyl N-Phenyl-N-[1-(2-phenylethyl)piperidin-4-yl]prop-2-enamide 82003-75-6
Alphamethylacetylfentanyl.svg α-Methylacetylfentanyl N-Phenyl-N-[1-(1-phenylpropan-2-yl)-4-piperidyl]acetamide 101860-00-8
Alphamethylbutyrfentanyl structure.png α-Methylbutyrfentanyl N-phenyl-N-[1-(1-phenylpropan-2-yl)-4-piperidyl]butanamide
Alphamethylfentanyl.svg α-Methylfentanyl (AMF) N-phenyl-N-[1-(1-phenylpropan-2-yl)-4-piperidyl]propanamide 79704-88-4
Alphamethylthiofentanyl.svg α-Methylthiofentanyl N-Phenyl-N-[1-(1-thiophen-2-ylpropan-2-yl)-4-piperidyl]propanamide 103963-66-2
Alphamethylbetahydroxyfentanyl structure.png α-Methyl-β-hydroxyfentanyl [10] N-[1-(1-hydroxy-1-phenylpropan-2-yl)piperidin-4-yl]-N-phenylpropanamide
Acetylfentanyl.svg Acetylfentanyl N-(1-Phenethylpiperidin-4-yl)-N-phenylacetamide 3258-84-2
Alfentanil-2D-skeletal.svg Alfentanyl N-{1-[2-(4-ethyl-5-oxo-4,5-dihydro-1H-1,2,3,4-tetrazol-1-yl)ethyl]-4-(methoxymethyl)piperidin-4-yl}-N-phenylpropanamide 71195-58-9
Benzodioxolefentanyl structure.png Benzodioxolefentanyl N-Phenyl-N-[1-(2-phenylethyl)piperidin-4-yl]-2H-1,3-benzodioxole-5-carboxamide
Benzoylfentanyl structure.png Benzoylfentanyl N-(1-Phenethylpiperidin-4-yl)-N-phenylbenzamide
Benzylfentanyl.svg Benzylfentanyl N-(1-Benzylpiperidin-4-yl)-N-phenylpropanamide 1474-02-8
Betahydroxyfentanyl.svg β-Hydroxyfentanyl N-[1-(2-Hydroxy-2-phenylethyl)piperidin-4-yl]-N-phenylpropanamide 78995-10-5
Betahydroxythiofentanyl.svg β-Hydroxythiofentanyl N-{1-[2-Hydroxy-2-(thiophen-2-yl)ethyl]piperidin-4-yl}-N-phenylpropanamide 1474-34-6
Beta-hydroxy-4-methylfentanyl structure.png β-Hydroxy-4-methylfentanyl N-[1-(2-hydroxy-2-phenylethyl)-4-methylpiperidin-4-yl]-N-phenylpropanamide
Betamethylfentanyl.svg β-Methylfentanyl N-Phenyl-N-[1-(2-phenylpropyl)piperidin-4-yl]propanamide 79146-56-8
Brorphine structure.png Brorphine 1-{1-[1-(4-bromophenyl)ethyl]piperidin-4-yl}-1,3-dihydro-2H-benzimidazol-2-one
Butyrfentanyl.png Butyrfentanyl (Bu-F, BUF) N-(1-(2-Phenylethyl)-4-piperidinyl)-N-phenylbutyramide 1169-70-6
Brifentanil Structural Formulae.png Brifentanyl N-[(3R,4S)-1-[2-(4-Ethyl-5-oxotetrazol-1-yl)ethyl] -3-methylpiperidin-4-yl]-N-(2-fluorophenyl)-2-methoxyacetamide 101345-71-5
Carfentanil.svg Carfentanyl Methyl 1-(2-phenylethyl)-4-[phenyl(propanoyl)amino]piperidine-4-carboxylate 59708-52-0
Cyclopentyl-F structure.png Cyclopentylfentanyl N-phenyl-N-[1-(2-phenylethyl)piperidin-4-yl]cyclopentanecarboxamide 2088918-01-6
Cyclopropylfentanyl structure.png Cyclopropylfentanyl N-[1-(2-Phenylethyl)piperidin-4-yl]-N-phenylcyclopropanecarboxamide 1169-68-2
Estrutura molecular do Psicofentanil (EAZ-91-5).png EAZ-91-05 (quinuclidin-3-yl) 4-[phenyl(propanoyl)amino]-1-[2-(indol-3-yl)ethyl]piperidine-4-carboxylate
Isobutyrfentanyl structure.png Isobutyrylfentanyl 2-methyl-N-phenyl-N-[1-(1-phenylpropan-2-yl)piperidin-4-yl]propanamide 119618-70-1
Isofentanyl structure.png Isofentanyl N-(1-Benzyl-3-methylpiperidin-4-yl)-N-phenylpropanamide 79278-40-3
Hoechst-Roussel 1984.svg Höchtanyl PC13306764
Homofentanyl structure.png Homofentanyl (N-phenylpropylnorfentanyl) N-phenyl-N-[1-(3-phenylpropyl)piperidin-4-yl]propanamide
Fentapridol.png Hybrid molecule containing features of both fentanyl & haloperidol[11] N-phenyl-N-{1-[4-(4-fluorophenyl)-4-oxobutyl]piperidin-4-yl}propanamide
Tranyltanyl.png trans-phenylcyclopropyl-norfentanyl 1-(trans-2-Phenylcyclopropyl)-4-(N-propionylanilino)piperidine 102504-49-4
Fentroline.png Pyridin-4-ylethyl-norfentanyl N-phenyl-N-[1-(2-pyridin-4-ylethyl)piperidin-4-yl]propanamide 1443-41-0
Furanylfentanyl.svg Furanylfentanyl (Fu-F, FUF) N-Phenyl-N-[1-(2-phenylethyl)piperidin-4-yl]furan-2-carboxamide 101345-66-8
Furanylfentanyl2 structure.png Furanylethylfentanyl (FUEF) N-[1-[2-(2-furanyl)ethyl]-4-piperidinyl]-N-phenyl-propanamide 802544-02-1
Homofentanyl.png Fentanyl 4-methylene analogue (WO 2007/093603) N-phenyl-N-{[1-(2-phenylethyl)piperidin-4-yl]methyl}propanamide
Lofentanil.svg Lofentanyl methyl (3S,4R)-3-methyl-1-(2-phenylethyl)-4-[phenyl(propionyl)amino]piperidine-4-carboxylate 61380-40-3
N-methylcarfentanil structure.png N-Methylnorcarfentanyl methyl 1-methyl-4-(N-phenylpropanamido)piperidine-4-carboxylate 59708-50-8
Methoxyacetylfentanyl structure.png Methoxyacetylfentanyl (MAF) 2-Methoxy-N-(1-phenethylpiperidin-4-yl)-N-phenylacetamide 101345-67-9
Metafluorofentanyl structure.png meta-fluorofentanyl N-(3-Fluorophenyl)-N-[1-(2-phenylethyl)-4-piperidinyl]-propanamide 90736-22-4
Mirfentanil.png Mirfentanyl N-[1-(2-Phenylethyl)piperidin-4-yl]-N-pyrazin-2-yl-2-furamide 117523-47-4
Ocfentanil.png Ocfentanyl N-(2-Fluorophenyl)-2-methoxy-N-[1-(2-phenylethyl)piperidin-4-yl]acetamide 101343-69-5
Ohmefentanyl.svg Ohmefentanyl N-[1-(2-hydroxy-2-phenylethyl)-3-methylpiperidin-4-yl]-N-phenylpropanamide 78995-14-9
Orthofluorofentanyl structure.png Orthofluorofentanyl N-(2-Fluorophenyl)-N-[1-(2-phenylethyl)-4-piperidinyl]-propanamide
Parafluoroisobutyrylbenzylfentanyl structure.png Parafluoroisobutyrylbenzylfentanyl N-[(1-benzylpiperidin-4-yl)methyl]-N-(4-fluorophenyl)-2-methylpropanamide
R-30490 structure.png R-30490 N-[4-(Methoxymethyl)-1-(2-phenylethyl)piperidin-4-yl]-N-phenylpropanamide 60618-49-7
Remifentanil2DCSDS.svg Remifentanyl methyl 1-(3-methoxy-3-oxopropyl)-4-(N-phenylpropanamido)piperidine-4-carboxylate 132875-61-7
Secofentanyl structure.png Secofentanyl N-phenyl-N-{4-[methyl(2-phenylethyl)amino]butan-2-yl}propanamide
Sufentanil.svg Sufentanil N-[4-(Methoxymethyl)-1-(2-thiofuran-2-ylethyl)-4-piperidyl]-N-phenylpropanamide 56030-54-7
Tetrahydrofuranylfentanyl structure.png Tetrahydrofuranylfentanyl N-Phenyl-N-[1-(2-phenylethyl)piperidin-4-yl]oxolane-2-carboxamide 2142571-01-3
Tetramethylcyclopropylfentanyl structure.png Tetramethylcyclopropylfentanyl 2,2,3,3-Tetramethyl-N-(1-phenethylpiperidin-4-yl)-N-phenylcyclopropane-1-carboxamide 2309383-11-5
Thenylfentanyl.svg Thenylfentanyl N-phenyl-N-{[1-(thiophen-2-ylmethyl)piperidin-4-yl]methyl}propanamide 117332-93-1
Formel von A-3080.png Thiafentanil methyl 4-(N-(2-methoxyacetyl)anilino)-1-(2-thiophen-2-ylethyl)piperidine-4-carboxylate 101345-60-2
Thiofentanyl.svg Thiofentanyl N-phenyl-N-{1-[2-(2-thienyl)ethyl]piperidin-4-yl}propanamide 1165-22-6
Trefentanil.png Trefentanyl N-{1-[2-(4-ethyl-5-oxo-4,5-dihydro-1H-tetrazol-1-yl)ethyl]-4-phenylpiperidin-4-yl}-N-(2-fluorophenyl)propanamide 120656-93-1
Fentanyl analog with dual opioid-SNDRI properties.png Trifluorofentanyl U.S. Patent 20,110,046,180
Valerylfentanyl.png Valerylfentanyl (VF) N-(1-(2-Phenylethyl)-4-piperidinyl)-N-phenylpentylamide 122882-90-0

Analogue controls

Several jurisdictions have implemented analogue law controls of fentanyl analogues in an attempt to pre-emptively ban novel derivatives before they appear on the market. One representative example is the New Zealand provisions enacted in 1988 in response to the first wave of fentanyl derivatives. This bans a set of structures as follows;

"Fentanyl analogues, in which the N-[1-(2-phenethyl)-4-piperidyl]aniline nucleus has additional radicals, either alone or in combination, attached as follows:

(a) an acetyl, propionyl, butenoyl or butanoyl radical, attached to the aniline nitrogen atom:

(b) 1 or more alkyl radicals, with up to 10 carbon atoms in total, attached to the ethyl moiety:

(c) any combination of up to 5 alkyl radicals and/or alkoxy radicals (each with up to 6 carbon atoms, including cyclic radicals) and/or halogen radicals, attached to each of the benzene rings."[12]

A more recent and somewhat broader example was introduced into US Federal legislation in 2018, covering the following structures;

"...fentanyl-related substances includes any substance not otherwise controlled in any schedule...that is structurally related to fentanyl by one or more of the following modifications:

  1. Replacement of the phenyl portion of the phenethyl group by any monocycle, whether or not further substituted in or on the monocycle;
  2. substitution in or on the phenethyl group with alkyl, alkenyl, alkoxyl, hydroxyl, halo, haloalkyl, amino or nitro groups;
  3. substitution in or on the piperidine ring with alkyl, alkenyl, alkoxyl, ester, ether, hydroxyl, halo, haloalkyl, amino or nitro groups;
  4. replacement of the aniline ring with any aromatic monocycle whether or not further substituted in or on the aromatic monocycle; and/or
  5. replacement of the N-propionyl group by another acyl group."[13]

See also

References

  1. ^ Mounteney J, Giraudon I, Denissov G, Griffiths P (July 2015). "Fentanyls: Are we missing the signs? Highly potent and on the rise in Europe". The International Journal on Drug Policy. 26 (7): 626–31. doi:10.1016/j.drugpo.2015.04.003. PMID 25976511.
  2. ^ Zawilska JB (2017). "An Expanding World of Novel Psychoactive Substances: Opioids". Frontiers in Psychiatry. 8: 110. doi:10.3389/fpsyt.2017.00110. PMC 5492455. PMID 28713291.
  3. ^ "Recommended Methods for the Identification and Analysis of Fentanyl and its Analogues in Biological Specimens" (PDF). United Nations Office on Drugs and Crime. November 2017.
  4. ^ Vardanyan RS, Hruby VJ (March 2014). "Fentanyl-related compounds and derivatives: current status and future prospects for pharmaceutical applications". Future Medicinal Chemistry. 6 (4): 385–412. doi:10.4155/fmc.13.215. PMC 4137794. PMID 24635521.
  5. ^ Armenian P, Vo KT, Barr-Walker J, Lynch KL (October 2017). "Fentanyl, fentanyl analogs and novel synthetic opioids: A comprehensive review" (Submitted manuscript). Neuropharmacology. 134 (Pt A): 121–132. doi:10.1016/j.neuropharm.2017.10.016. PMID 29042317.
  6. ^ Skulska A, Kała M, Parczewski A. Fentanyl and its analogs in the forensic laboratory. Medical and analytical problems. Probl Forensic Sci. 2004;59:127-42.
  7. ^ Misailidi, Nektaria; Papoutsis, Ioannis; Nikolaou, Panagiota; Dona, Artemisia; Spiliopoulou, Chara; Athanaselis, Sotiris (January 2018). "Fentanyls continue to replace heroin in the drug arena: the cases of ocfentanil and carfentanil". Forensic Toxicology. 36 (1): 12–32. doi:10.1007/s11419-017-0379-4. ISSN 1860-8965. PMC 5754389. PMID 29367860.
  8. ^ Drug Enforecement Administration, Department of Justice (2018). "Schedules of Controlled Substances:Temporary Placement of Fentanyl-Related Substances in Schedule I. Temporary amendment; temporary scheduling order". Federal Register. 83 (25): 5188–92. PMID 29932611.
  9. ^ Lalinde N, Moliterni J, Wright D, Spencer HK, Ossipov MH, Spaulding TC, Rudo FG (October 1990). "Synthesis and pharmacological evaluation of a series of new 3-methyl-1,4-disubstituted-piperidine analgesics". Journal of Medicinal Chemistry. 33 (10): 2876–82. doi:10.1021/jm00172a032. PMID 2170652.
  10. ^ Barceloux DG. Medical Toxicology of Drug Abuse: Synthesized Chemicals and Psychoactive Plants. Wiley, 2012. Barceloux, Donald G (2012-03-20). "Medical Toxicology of Drug Abuse: Synthesized Chemicals and Psychoactive Plants". ISBN 978-0471727606. Cite journal requires |journal= (help)
  11. ^ US granted 3161637, Janssen PA, "1-(gamma-aroyl-propyl)-4-(nu-arylcarbonyl amino) piperidines and related compounds", issued 15 December 1964, assigned to Janssen Resarch Labs 
  12. ^ "Schedule 3 Class C Controlled Drugs; Part 7: Fentanyl analogues". New Zealand Misuse of Drugs Act 1975.
  13. ^ "Schedules of Controlled Substances: Temporary Placement of Fentanyl-Related Substances in Schedule I". United States Federal Register.

External links