Forensic Toxicology

, Volume 31, Issue 2, pp 281–291 | Cite as

[1-(Tetrahydropyran-4-ylmethyl)-1H-indol-3-yl]-(2,2,3,3-tetramethylcyclopropyl)methanone: a new synthetic cannabinoid identified on the drug market

  • Dariusz Zuba
  • Bogna Geppert
  • Karolina Sekuła
  • Czesław Żaba
Original Article


A new synthetic cannabinoid, [1-(tetrahydropyran-4-ylmethyl)-1H-indol-3-yl]-(2,2,3,3-tetramethylcyclopropyl)methanone, was identified in several resinous samples seized by law enforcement officers in Poland. Its identification was based on liquid chromatography–electrospray ionization–quadrupole time-of-flight–mass spectrometry, gas chromatography–electron ionization–mass spectrometry, one-dimensional and two-dimensional nuclear magnetic resonance spectroscopy, and Fourier-transform infrared spectroscopy. The reported substance was first developed by Abbott Laboratories and patented under the name “A-834,735”. It is a potent agonist of both CB1 and CB2 receptors. Although A-834,735 shows moderate selectivity to CB2 receptor, it exhibits a CB1 affinity similar to that of ∆9-tetrahydrocannabinol. The drug has recently become available in online shops. To our knowledge, this is the first report to disclose a synthetic cannabinoid containing a (tetrahydropyran-4-yl)methyl structure in products seized from the drug market.


Synthetic cannabinoid A-834,735 [1-(Tetrahydropyran-4-ylmethyl)-1H-indol-3-yl]-(2,2,3,3-tetramethylcyclopropyl)methanone Herbal highs LC–ESI–QTOF–MS NMR identification 


Conflict of interest

There are no financial or other relations that could lead to a conflict of interest.


  1. 1.
    EMCDDA and Europol (2012) EU drug markets report: a strategic analysis. Publications Office of the European Union, LuxembourgGoogle Scholar
  2. 2.
    Auwärter V, Dresen S, Weinmann W, Müller M, Pütz M, Ferreiros N (2009) ‘Spice’ and other herbal blends: harmless incense or cannabinoid designer drugs? J Mass Spectrom 44:832–837PubMedCrossRefGoogle Scholar
  3. 3.
    EMCDDA (2011) Online sales of new psychoactive substances/‘legal highs’: summary of results from the 2011 multilingual snapshots. European Monitoring Centre for Drugs and Drug Addiction, LisbonGoogle Scholar
  4. 4.
    EMCDDA (2012) Statistical bulletin 2012. European Monitoring Centre for Drugs and Drug Addiction, LisbonGoogle Scholar
  5. 5.
    Zuba D, Byrska B (2012) Prevalence and co-existence of active components of ‘legal highs’. Drug Test Anal. doi: 10.1002/dta.1365 Google Scholar
  6. 6.
    Kikura-Hanajiri R, Uchiyama N, Kawamura M, Goda Y (2013) Changes in the prevalence of synthetic cannabinoids and cathinone derivatives in Japan until early 2012. Forensic Toxicol 31:44–53CrossRefGoogle Scholar
  7. 7.
    Auwärter V, Kneisel S, Hutter M, Thierauf A (2012) Synthetische Cannabinoide. Rechtsmedizin 22:259–271CrossRefGoogle Scholar
  8. 8.
    Nakajima J, Takahashi M, Seto T, Kanai C, Suzuki J, Yoshida M, Hamano T (2011) Identification and quantitation of two benzoylindoles AM-694 and (4-methoxyphenyl)(1-pentyl-1H-indol-3-yl)methanone, and three cannabimimetic naphthoylindoles JWH-210, JWH-122, and JWH-019 as adulterants in illegal products obtained via the Internet. Forensic Toxicol 29:95–110CrossRefGoogle Scholar
  9. 9.
    Uchiyama N, Kawamura M, Kikura-Hanajiri R, Goda Y (2011) Identification and quantitation of two cannabimimetic phenylacetylindoles JWH-251 and JWH-250, and four cannabimimetic naphthoylindoles JWH-081, JWH-015, JWH-200, and JWH-073 as designer drugs in illegal products. Forensic Toxicol 29:25–37CrossRefGoogle Scholar
  10. 10.
    Nakajima J, Takahashi M, Nonaka R, Seto T, Suzuki J, Yoshida M, Kanai C, Hamano T (2011) Identification and quantitation of a benzoylindole (2-methoxyphenyl)(1-pentyl-1H-indol-3-yl)methanone and a naphthoylindole 1-(5-fluoropentyl-1H-indol-3-yl)-(naphthalene-1-yl)methanone (AM-2201) found in illegal products obtained via the Internet and their cannabimimetic effects evaluated by in vitro [35S]GTPγS binding assays. Forensic Toxicol 29:132–141CrossRefGoogle Scholar
  11. 11.
    Nakajima J, Takahashi M, Seto T, Yoshida M, Kanai C, Suzuki J, Hamano T (2012) Identification and quantitation of two new naphthoylindole drugs-of-abuse, (1-(5-hydroxypentyl)-1H-indol-3-yl)(naphthalen-1-yl)methanone (AM-2202) and (1-(4-pentenyl)-1H-indol-3-yl)(naphthalen-1-yl)methanone, with other synthetic cannabinoids in unregulated “herbal” products circulated in the Tokyo area. Forensic Toxicol 30:33–44CrossRefGoogle Scholar
  12. 12.
    Uchiyama N, Kawamura M, Kikura-Hanajiri R, Goda Y (2012) Identification of two new-type synthetic cannabinoids, N-(1-adamantyl)-1-pentyl-1H-indole-3-carboxamide (APICA) and N-(1-adamantyl)-1-pentyl-1H-indazole-3-carboxamide (APINACA), and detection of five synthetic cannabinoids, AM-1220, AM-2233, AM-1241, CB-13 (CRA-13), and AM-1248, as designer drugs in illegal products. Forensic Toxicol 30:114–125CrossRefGoogle Scholar
  13. 13.
    Kneisel S, Bisel P, Brecht V, Broecker S, Müller M, Auwärter V (2012) Identification of the cannabimimetic AM-1220 and its azepane isomer (N-methylazepan-3-yl)-3-(1-naphthoyl)indole in a research chemical and several herbal mixtures. Forensic Toxicol 30:126–134CrossRefGoogle Scholar
  14. 14.
    Moosmann B, Kneisel S, Girreser U, Brecht V, Westphal F, Auwärter V (2012) Separation and structural characterization of the synthetic cannabinoids JWH-412 and 1-[(5-fluoropentyl)-1H-indol-3yl]-(4-methylnaphthalen-1-yl)methanone using GC-MS, NMR analysis and a flash chromatography system. Forensic Sci Int 220:e17–e22PubMedCrossRefGoogle Scholar
  15. 15.
    Uchiyama N, Matsuda S, Wakana D, Kikura-Hanajiri R, Goda Y (2013) New cannabimimetic indazole derivatives, N-(1-amino-3-methyl-1-oxobutan-2-yl)-1-pentyl-1H-indazole-3-carboxamide (AB-PINACA) and N-(1-amino-3-methyl-1-oxobutan-2-yl)-1-(4-fluorobenzyl)-1H-indazole-3-carboxamide (AB-FUBINACA) identified as designer drugs in illegal products. Forensic Toxicol 31:93–100CrossRefGoogle Scholar
  16. 16.
    Uchiyama N, Matsuda S, Kawamura M, Kikura-Hanajiri R, Goda Y (2013) Two new-type cannabimimetic quinolinyl carboxylates, QUPIC and QUCHIC, two new cannabimimetic carboxamide derivatives, ADB-FUBINACA and ADBICA, and five synthetic cannabinoids detected with a thiophene derivative α-PVT and an opioid receptor agonist AH-7921 identified in illegal products. Forensic Toxicol. doi: 10.1007/s11419-013-0182-9 Google Scholar
  17. 17.
    Choi H, Heo S, Kim E, Hwang BY, Lee C, Lee J (2013) Identification of (1-pentylindol-3-yl)-(2,2,3,3-tetramethylcyclopropyl)methanone and its 5-pentyl fluorinated analog in herbal incense seized for drug trafficking. Forensic Toxicol 31:86–92CrossRefGoogle Scholar
  18. 18.
    Kavanagh P, Grigoryev A, Savchuk S, Mikhura I, Formanovsky A (2013) UR-144 in products sold via the Internet: identification of related compounds and characterization of pyrolysis products. Drug Test Anal. doi: 10.1002/dta.1456 Google Scholar
  19. 19.
    Huffman JW, Dai D (1994) Design, synthesis and pharmacology of cannabimimetic indoles. Bioorg Med Chem Lett 4:563–566CrossRefGoogle Scholar
  20. 20.
    Huffman JW, Padgett LW (2005) Recent developments in the medicinal chemistry of cannabimimetic indoles, pyrroles and indenes. Curr Med Chem 12:1395–1411PubMedCrossRefGoogle Scholar
  21. 21.
    Eissenstat MA, Bell MR, D’Ambra TE, Alexander EJ, Daum SJ, Ackerman JH, Gruett MD, Kumar V, Estep KG (1995) Aminoalkylindoles: structure–activity relationships of novel cannabinoid mimetics. J Med Chem 38:3094–3105PubMedCrossRefGoogle Scholar
  22. 22.
    Lin S, Khanolkar AD, Fan P, Goutopoulos A, Qin C, Papahadjis D, Makriyannis A (1998) Novel analogues of arachidonylethanolamide (anandamide): affinities for the CB1 and CB2 cannabinoid receptors and metabolic stability. J Med Chem 41:5353–5361PubMedCrossRefGoogle Scholar
  23. 23.
    Frost JM, Dart MJ, Tietje KR, Garrison TR, Grayson GK, Daza AV, El-Kouhen OF, Miller LN, Li L, Yao BB, Hsieh GC, Pai M, Zhu CZ, Chandran P, Meyer MD (2008) Indol-3-yl-tetramethylcyclopropyl ketones: effects of indole ring substitution on CB2 cannabinoid receptor activity. J Med Chem 51:1904–1912PubMedCrossRefGoogle Scholar
  24. 24.
    Uchiyama N, Kawamura M, Kikura-Hanajiri R, Goda Y (2013) URB-754: a new class of designer drug and 12 synthetic cannabinoids detected in illegal products. Forensic Sci Int 227:21–32PubMedCrossRefGoogle Scholar
  25. 25.
    Murineddu G, Asproni B, Pinna GA (2012) A survey of recent patents on CB2 agonists in the management of pain. Recent Pat CNS Drug Discov 7:4–24PubMedCrossRefGoogle Scholar
  26. 26.
    Willis PG, Pavlova OA, Chefer SI, Vaupel DB, Mukhin AG, Horti AG (2005) Synthesis and structure–activity relationship of a novel series of aminoalkylindoles with potential for imaging the neuronal cannabinoid receptor by positron emission tomography. J Med Chem 48:5813–5822PubMedCrossRefGoogle Scholar
  27. 27.
    Yao BB, Hsieh GC, Frost JM, Fan Y, Garrison TR, Daza AV, Grayson GK, Zhu CZ, Pai M, Chandran P, Salyers AK, Wensink EJ, Honore P, Sullivan JP, Dart MJ, Meyer MD (2008) In vitro and in vivo characterization of A-796260: a selective cannabinoid CB2 receptor agonist exhibiting analgesic activity in rodent pain models. Br J Pharmacol 153:390–401PubMedCrossRefGoogle Scholar
  28. 28.
    Worm K, Dolle RE (2009) Simultaneous optimization of potency, selectivity and physicochemical properties for cannabinoid CB2 ligands. Curr Pharm Design 15:3345–3366CrossRefGoogle Scholar
  29. 29.
    Sekuła K, Zuba D, Stanaszek R (2012) Identification of naphthoylindoles acting on cannabinoid receptors based on their fragmentation patterns under ESI-QTOFMS. J Mass Spectrom 47:632–643PubMedCrossRefGoogle Scholar
  30. 30.
    Wong HNC, Hon MY, Tse CW, Yip YC, Tanko J, Hudlicky T (1989) Use of cyclopropanes and their derivatives in organic synthesis. Chem Rev 89:165–198CrossRefGoogle Scholar
  31. 31.
    Coates J (2000) Interpretation of infrared spectra: a practical approach. In: Meyers RA (ed) Encyclopedia of analytical chemistry. Wiley, Chichester, pp 10815–10837Google Scholar
  32. 32.
    Mauler F, Mittendorf J, Horváth E, De Vry J (2002) Characterization of the diarylether sulfonylester (-)-(R)-3-(2-hydroxymethylindanyl-4-oxy)phenyl-4,4,4-trifluoro-1-sulfonate (BAY 38–7271) as a potent cannabinoid receptor agonist with neuroprotective properties. J Pharmacol Exp Ther 302:359–368PubMedCrossRefGoogle Scholar
  33. 33.
    Frost JM, Dart MJ, Tietje KR, Garrison TR, Grayson GK, Daza AV, El-Kouhen OF, Yao BB, Hsieh GC, Pai M, Zhu CZ, Chandran P, Meyer MD (2010) Indol-3-ylcycloalkyl ketones: effects of N1 substituted indole side chain variations on CB(2) cannabinoid receptor activity. J Med Chem 53:295–315PubMedCrossRefGoogle Scholar
  34. 34.

Copyright information

© Japanese Association of Forensic Toxicology and Springer Japan 2013

Authors and Affiliations

  • Dariusz Zuba
    • 1
  • Bogna Geppert
    • 2
  • Karolina Sekuła
    • 1
  • Czesław Żaba
    • 2
  1. 1.Institute of Forensic ResearchKrakówPoland
  2. 2.Chair and Department of Forensic MedicineThe Poznań University of Medical SciencesPoznańPoland

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