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
2,5-Dimethylfentanyl N-[2,5-Dimethyl-1-(2-phenylethyl)piperidin-4-yl]-N-phenylpropanamide 42045-97-6
2,2'-Difluorofentanyl N-(2-Fluorophenyl)-N-[1-(2-[2-fluorophenyl]ethyl)-4-piperidinyl]-propanamide
3-Allylfentanyl N-[(3S,4R)-1-Phenethyl-3-prop-2-enylpiperidin-4-yl]-N-phenylpropanamide 82208-84-2
3-Fluorofentanyl (NFEPP) N-(3-Fluoro-1-phenethylpiperidin-4-yl)-N-phenylpropionamide 1422952-84-8
3-Furanylfentanyl (3FUF) N-Phenyl-N-[1-(2-phenylethyl)piperidin-4-yl]furan-3-carboxamide 101343-82-2
3-Methylbutyrfentanyl N-[3-Methyl-1-(2-phenylethyl)piperidin-4-yl]-N-phenylbutanamide 97605-09-9
3-Methylfentanyl (3-MF) N-(3-methyl-1-phenethyl-4-piperidyl)-N-phenyl-propanamide 42045-86-3
3-Methylfuranylfentanyl[9] (3MFUF, TMFUF) N-Phenyl-N-[3-methyl-1-(2-phenylethyl)piperidin-4-yl]furan-2-carboxamide
3-Methylthiofentanyl N-{3-Methyl-1-[2-(2-thienyl)ethyl]piperidin-4-yl}-N-phenylpropanamide 86052-04-2
3-Phenylpropanoylfentanyl N-Phenyl-N-[1-(2-phenylethyl)piperidin-4-yl]-3-phenylpropanamide 79279-02-0
4-Fluorobutyrfentanyl (4-FBF) N-(4-Fluorophenyl)-N-[1-(2-phenylethyl)-4-piperidinyl]-butanamide 244195-31-1
4-Chloroisobutyrylfentanyl (4-CIBF) 2-Methyl-N-(4-chlorophenyl)-N-[1-(1-phenylpropan-2-yl)piperidin-4-yl]propanamide 244195-34-4
4-Fluoroisobutyrfentanyl (4-FIBF) N-(4-Fluorophenyl)-N-[1-(2-phenylethyl)-4-piperidinyl]-isobutanamide 244195-32-2
4-Fluorofentanyl N-(4-fluorophenyl)-N-[1-(2-phenylethyl)piperidin-4-yl]propanamide 90736-23-5
para-fluorofuranylfentanyl (p-F-Fu-F) N-(1-phenethylpiperidin-4-yl)-N-(4-fluorophenyl)furan-2-carboxamide 1802489-71-9
para-chlorofuranylfentanyl (p-Cl-Fu-F) N-(1-phenethylpiperidin-4-yl)-N-(4-chlorophenyl)furan-2-carboxamide
ortho-methylfuranylfentanyl (o-Me-Fu-F) N-(1-phenethylpiperidin-4-yl)-N-(o-tolyl)furan-2-carboxamide
ortho-methoxyfuranylfentanyl (o-MeO-Fu-F) N-(1-phenethylpiperidin-4-yl)-N-(2-methoxyphenyl)furan-2-carboxamide
ortho-isopropylfuranylfentanyl (o-iPr-Fu-F) N-(1-phenethylpiperidin-4-yl)-N-(2-isopropylphenyl)furan-2-carboxamide
4-Phenylfentanyl N-Phenyl-N-[4-phenyl-1-(2-phenylethyl)piperidin-4-yl]propanamide 120448-97-7
4-Methoxybutyrfentanyl N-(4-Methoxyphenyl)-N-[1-(2-phenylethyl)-4-piperidinyl]-butanamide 2088842-68-4
4-Methylphenethylacetylfentanyl N-[1-[2-(4-Methylphenyl)ethyl]-4-piperidinyl]-N-phenylacetamide 1071703-95-1
Acrylfentanyl N-Phenyl-N-[1-(2-phenylethyl)piperidin-4-yl]prop-2-enamide 82003-75-6
α-Methylacetylfentanyl N-Phenyl-N-[1-(1-phenylpropan-2-yl)-4-piperidyl]acetamide 101860-00-8
α-Methylbutyrfentanyl N-phenyl-N-[1-(1-phenylpropan-2-yl)-4-piperidyl]butanamide
α-Methylfentanyl (AMF) N-phenyl-N-[1-(1-phenylpropan-2-yl)-4-piperidyl]propanamide 79704-88-4
α-Methylthiofentanyl N-Phenyl-N-[1-(1-thiophen-2-ylpropan-2-yl)-4-piperidyl]propanamide 103963-66-2
α-Methyl-β-hydroxyfentanyl [10] N-[1-(1-hydroxy-1-phenylpropan-2-yl)piperidin-4-yl]-N-phenylpropanamide
Acetylfentanyl N-(1-Phenethylpiperidin-4-yl)-N-phenylacetamide 3258-84-2
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 N-Phenyl-N-[1-(2-phenylethyl)piperidin-4-yl]-2H-1,3-benzodioxole-5-carboxamide
Benzoylfentanyl N-(1-Phenethylpiperidin-4-yl)-N-phenylbenzamide
Benzylfentanyl N-(1-Benzylpiperidin-4-yl)-N-phenylpropanamide 1474-02-8
β-Hydroxyfentanyl N-[1-(2-Hydroxy-2-phenylethyl)piperidin-4-yl]-N-phenylpropanamide 78995-10-5
β-Hydroxythiofentanyl N-{1-[2-Hydroxy-2-(thiophen-2-yl)ethyl]piperidin-4-yl}-N-phenylpropanamide 1474-34-6
β-Hydroxy-4-methylfentanyl N-[1-(2-hydroxy-2-phenylethyl)-4-methylpiperidin-4-yl]-N-phenylpropanamide
β-Methylfentanyl N-Phenyl-N-[1-(2-phenylpropyl)piperidin-4-yl]propanamide 79146-56-8
Brorphine 1-{1-[1-(4-bromophenyl)ethyl]piperidin-4-yl}-1,3-dihydro-2H-benzimidazol-2-one
Butyrfentanyl (Bu-F, BUF) N-(1-(2-Phenylethyl)-4-piperidinyl)-N-phenylbutyramide 1169-70-6
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
Carfentanyl Methyl 1-(2-phenylethyl)-4-[phenyl(propanoyl)amino]piperidine-4-carboxylate 59708-52-0
Cyclopentylfentanyl N-phenyl-N-[1-(2-phenylethyl)piperidin-4-yl]cyclopentanecarboxamide 2088918-01-6
Cyclopropylfentanyl N-[1-(2-Phenylethyl)piperidin-4-yl]-N-phenylcyclopropanecarboxamide 1169-68-2
EAZ-91-05 (quinuclidin-3-yl) 4-[phenyl(propanoyl)amino]-1-[2-(indol-3-yl)ethyl]piperidine-4-carboxylate
Isobutyrylfentanyl 2-methyl-N-phenyl-N-[1-(1-phenylpropan-2-yl)piperidin-4-yl]propanamide 119618-70-1
Isofentanyl N-(1-Benzyl-3-methylpiperidin-4-yl)-N-phenylpropanamide 79278-40-3
Höchtanyl PC13306764
Homofentanyl (N-phenylpropylnorfentanyl) N-phenyl-N-[1-(3-phenylpropyl)piperidin-4-yl]propanamide
Hybrid molecule containing features of both fentanyl & haloperidol[11] N-phenyl-N-{1-[4-(4-fluorophenyl)-4-oxobutyl]piperidin-4-yl}propanamide
trans-phenylcyclopropyl-norfentanyl 1-(trans-2-Phenylcyclopropyl)-4-(N-propionylanilino)piperidine 102504-49-4
Pyridin-4-ylethyl-norfentanyl N-phenyl-N-[1-(2-pyridin-4-ylethyl)piperidin-4-yl]propanamide 1443-41-0
Furanylfentanyl (Fu-F, FUF) N-Phenyl-N-[1-(2-phenylethyl)piperidin-4-yl]furan-2-carboxamide 101345-66-8
Furanylethylfentanyl (FUEF) N-[1-[2-(2-furanyl)ethyl]-4-piperidinyl]-N-phenyl-propanamide 802544-02-1
Fentanyl 4-methylene analogue (WO 2007/093603) N-phenyl-N-{[1-(2-phenylethyl)piperidin-4-yl]methyl}propanamide
Lofentanyl methyl (3S,4R)-3-methyl-1-(2-phenylethyl)-4-[phenyl(propionyl)amino]piperidine-4-carboxylate 61380-40-3
N-Methylnorcarfentanyl methyl 1-methyl-4-(N-phenylpropanamido)piperidine-4-carboxylate 59708-50-8
Methoxyacetylfentanyl (MAF) 2-Methoxy-N-(1-phenethylpiperidin-4-yl)-N-phenylacetamide 101345-67-9
meta-fluorofentanyl N-(3-Fluorophenyl)-N-[1-(2-phenylethyl)-4-piperidinyl]-propanamide 90736-22-4
Mirfentanyl N-[1-(2-Phenylethyl)piperidin-4-yl]-N-pyrazin-2-yl-2-furamide 117523-47-4
Ocfentanyl N-(2-Fluorophenyl)-2-methoxy-N-[1-(2-phenylethyl)piperidin-4-yl]acetamide 101343-69-5
Ohmefentanyl N-[1-(2-hydroxy-2-phenylethyl)-3-methylpiperidin-4-yl]-N-phenylpropanamide 78995-14-9
Orthofluorofentanyl N-(2-Fluorophenyl)-N-[1-(2-phenylethyl)-4-piperidinyl]-propanamide
Parafluoroisobutyrylbenzylfentanyl N-[(1-benzylpiperidin-4-yl)methyl]-N-(4-fluorophenyl)-2-methylpropanamide
R-30490 N-[4-(Methoxymethyl)-1-(2-phenylethyl)piperidin-4-yl]-N-phenylpropanamide 60618-49-7
Remifentanyl methyl 1-(3-methoxy-3-oxopropyl)-4-(N-phenylpropanamido)piperidine-4-carboxylate 132875-61-7
Secofentanyl N-phenyl-N-{4-[methyl(2-phenylethyl)amino]butan-2-yl}propanamide
Sufentanil N-[4-(Methoxymethyl)-1-(2-thiofuran-2-ylethyl)-4-piperidyl]-N-phenylpropanamide 56030-54-7
Tetrahydrofuranylfentanyl N-Phenyl-N-[1-(2-phenylethyl)piperidin-4-yl]oxolane-2-carboxamide 2142571-01-3
Tetramethylcyclopropylfentanyl 2,2,3,3-Tetramethyl-N-(1-phenethylpiperidin-4-yl)-N-phenylcyclopropane-1-carboxamide 2309383-11-5
Thenylfentanyl N-phenyl-N-{[1-(thiophen-2-ylmethyl)piperidin-4-yl]methyl}propanamide 117332-93-1
Thiafentanil methyl 4-(N-(2-methoxyacetyl)anilino)-1-(2-thiophen-2-ylethyl)piperidine-4-carboxylate 101345-60-2
Thiofentanyl N-phenyl-N-{1-[2-(2-thienyl)ethyl]piperidin-4-yl}propanamide 1165-22-6
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
Trifluorofentanyl U.S. Patent 20,110,046,180
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.
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