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][6] 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,[7][8][9][10][11] 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 Administration 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.[12]

Chemical structures of various fentanyl analoguesEdit

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[13] (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) [14] 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
  para-Hydroxy‐butyrylfentanyl [15] N-(4-hydroxyphenyl)-N-[1-(2-phenylethyl)-4-piperidinyl]-butanamide
  4-Methylphenethylacetylfentanyl [16] 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[17] 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 [18] 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 [19] 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
  Crotonylfentanyl N-Phenyl-N-[1-(2-phenylethyl)-4-piperidinyl]-2-butenamide 760930-59-4
  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
  Homofentanyl (N-phenylpropylnorfentanyl) [20] N-phenyl-N-[1-(3-phenylpropyl)piperidin-4-yl]propanamide 59708-54-2
  Hybrid molecule containing features of both fentanyl & haloperidol[21] 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
  IQMF-4 [22] N-[1-(2-Phenylethyl)piperidin-4-yl]-N-(1-phenylpyrazol-3-yl)prop-2-enamide
  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 910616-29-4
  Parafluoroisobutyrylbenzylfentanyl N-[(1-benzylpiperidin-4-yl)methyl]-N-(4-fluorophenyl)-2-methylpropanamide
  Pyrrole-fentanyl [23] N-[1-(2-Phenylethyl)piperidin-4-yl]-N-pyrrol-1-ylpropanamide
  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
  RR49 [24] N-{1-[2-Fluoro-2-(2-fluorophenyl)ethyl]piperidin-4-yl}-N-phenylpropanamide
  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 [25] N-(3,4-difluorophenyl)-N-[1-(2-[4-fluorophenyl]ethyl)-4-piperidinyl]-propanamide
  3,4-dichloro-4''-methoxyfentanyl N-(3,4-dichlorophenyl)-N-[1-(2-[4-methoxyphenyl]ethyl)-4-piperidinyl]-propanamide
  Valerylfentanyl (VF) N-(1-(2-Phenylethyl)-4-piperidinyl)-N-phenylpentylamide 122882-90-0

Analogue controlsEdit

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."[26]

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."[27]

See alsoEdit

ReferencesEdit

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  6. ^ Fentanyl-related substances with no known legitimate uses. International Narcotics Control Board, 24 June 2018
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  13. ^ 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.
  14. ^ Le AD, Alzghari SK (October 2019). "Systematic review of the clinical consequences of butyrfentanyl and corresponding analogues". Interdisciplinary Toxicology. 12 (2): 83–88. doi:10.2478/intox-2019-0009. PMC 7071838. PMID 32206028.
  15. ^ Oldenhof S, Ten Pierick A, Bruinsma J, Eustace S, Hulshof J, van den Berg J, Hoitink M (January 2020). "Identification of a novel fentanyl analog: p-Hydroxy-butyrylfentanyl". Drug Testing and Analysis. 12 (1): 152–155. doi:10.1002/dta.2695. PMID 31518047.
  16. ^ Moore JM, Allen AC, Cooper DA, Carr SM (July 1986). "Determination of fentanyl and related compounds by capillary gas chromatography with electron capture detection". Analytical Chemistry. 58 (8): 1656–60. doi:10.1021/ac00121a013. PMID 3752503.
  17. ^ Barceloux DG (2012). Medical Toxicology of Drug Abuse: Synthesized Chemicals and Psychoactive Plants. Wiley. ISBN 978-0471727606.
  18. ^ Varshneya NB, Walentiny DM, Moisa LT, Walker TD, Akinfiresoye LR, Beardsley PM (June 2019). "Opioid-like antinociceptive and locomotor effects of emerging fentanyl-related substances". Neuropharmacology. 151: 171–179. doi:10.1016/j.neuropharm.2019.03.023. PMID 30904478. S2CID 84182661.
  19. ^ Kennedy NM, Schmid CL, Ross NC, Lovell KM, Yue Z, Chen YT, et al. (October 2018). "Optimization of a Series of Mu Opioid Receptor (MOR) Agonists with High G Protein Signaling Bias". Journal of Medicinal Chemistry. 61 (19): 8895–8907. doi:10.1021/acs.jmedchem.8b01136. PMC 6386185. PMID 30199635.
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External linksEdit