2-Fluorodeschloroketamine

Chemical compound December 2020 2-(2-Fluorophenyl)-2-methylamino-cyclohexanone 2-Fluorodeschloroketamine.svg skin-invert-image 220 Illegal in Italy, Japan, Latvia, Singapore, Sweden and Switzerland Schedule I Anlage II Class B 111982-50-4 13771618 43515873 D57WIH0RIT 13 16 1 1 1 CNC1(CCCCC1=O)c2ccccc2F 1S/C13H16FNO/c1-15-13(9-5-4-8-12(13)16)10-6-2-3-7-11(10)14/h2-3,6-7,15H,4-5,8-9H2,1H3 PHFAGYYTDLITTB-UHFFFAOYSA-N 2-Fluorodeschloroketamine (also known as 2'-Fl-2-Oxo-PCM, fluoroketamine, and 2-FDCK) is a dissociative anesthetic Moghimi A, Rahmani S, Zare R, Sadeghzadeh M 2014-07-18 Synthesis of 2-(2-Fluorophenyl)-2-methylamino-Cyclohexanone as a New Ketamine Derivative Synthetic Communications en 44 14 2021–2028 10.1080/00397911.2014.885053 98475552 https://figshare.com/articles/journal_contribution/1003833 related to ketamine. Its sale and use as a designer drug has been reported in various countries. Davidsen AB, Mardal M, Holm NB, Andreasen AK, Johansen SS, Noble C, Dalsgaard P, Linnet K 6 Ketamine analogues: Comparative toxicokinetic in vitro-in vivo extrapolation and quantification of 2-fluorodeschloroketamine in forensic blood and hair samples Journal of Pharmaceutical and Biomedical Analysis 180 113049 February 2020 31881397 10.1016/j.jpba.2019.113049 209499229 Wang PF, Neiner A, Lane TR, Zorn KM, Ekins S, Kharasch ED Halogen Substitution Influences Ketamine Metabolism by Cytochrome P450 2B6: In Vitro and Computational Approaches Molecular Pharmaceutics 16 2 898–906 February 2019 30589555 9121441 10.1021/acs.molpharmaceut.8b01214 Tang MH, Li TC, Lai CK, Chong YK, Ching CK, Mak TW Emergence of new psychoactive substance 2-fluorodeschloroketamine: Toxicology and urinary analysis in a cluster of patients exposed to ketamine and multiple analogues Forensic Science International 312 110327 July 2020 32460225 10.1016/j.forsciint.2020.110327 218954528 It is an analogue of ketamine where the chlorine group has been replaced by fluorine. Due to its recent emergence, the pharmacological specifics of the compound are mostly unclear, but effects are reported to be similar to its parent compound, ketamine. History The synthesis of 2-FDCK was first described in a 2013 paper as part of a larger effort to synthesize and evaluate new anesthetic drugs based on ketamine and its analogues. Ketamine itself was first introduced in 1964 and was approved for clinical use in 1970. Since then it has become one of the most important and applicable general anesthetics as well as a popular recreational drug. The use of 2-FDCK as a research chemical has been reported in various countries. Li C, Lai CK, Tang MH, Chan CC, Chong YK, Mak TW Ketamine analogues multiplying in Hong Kong Hong Kong Medical Journal = Xianggang Yi Xue Za Zhi 25 2 169 April 2019 30971512 10.12809/hkmj197863 free European Monitoring Centre for Drugs and Drug Addiction (2017), EMCDDA–Europol 2016 Annual Report on the implementation of Council Decision 2005/387/JHA, Implementation reports, Publications Office of the European Union, Luxembourg. Many of these new psychoactive substances (NPS) appear on the drug market in order to circumvent existing drug policies. 2-FDCK was first formally notified by the EMCDDA in 2016, alongside 65 other new substances. Due to its recent appearance, little research has been done on the compound so far. In January 2023, Israeli Biotech company "Clearmind Medicine Inc." announced the successful completion of a preclinical study examining 2-FDCK in a rat model of depression, with the compound outperforming ketamine in longevity of antidepressant effect.Israeli Biotech Clearmind Medicine Announces Positive Pre-Clinical Results Treating Major Depression With a Novel Ketamine-Based Compound https://www.globenewswire.com/en/news-release/2023/01/31/2598573/0/en/Israeli-Biotech-Clearmind-Medicine-Announces-Positive-Pre-Clinical-Results-Treating-Major-Depression-With-a-Novel-Ketamine-Based-Compound.html January 31, 2023 February 26, 2024 Chemistry Structure The full chemical name of 2-FDCK is 2-(2-fluorophenyl)-2-(methylamino)cyclohexan-1-one.class=skin-invert-image|thumb|494x494px|Preparation of 2-FDCK from fluorobenzonitrile. 2-FDCK belongs to a class of compounds called arylcyclohexylamines which contains various other drugs such as PCP and ketamine. Their general structure consists of a cyclohexylamine unit with an aryl group attached to the same carbon as the amine. 2-FDCK has an o-fluorophenyl group as an aryl substituent and the amine group is methylated. The cyclohexyl ring features a ketone group next to the amine position. The chemical structure of 2-FDCK differs from ketamine only in that there is a fluorine atom attached to the phenyl group. Ketamine has a chlorine atom in that position. National Center for Biotechnology Information (2021). PubChem Compound Summary for CID 13771618, Fluoroketamine 7 March 2021 https://pubchem.ncbi.nlm.nih.gov/compound/Fluoroketamine Synthesis 2-FDCK can be synthesized in a five-step reaction process. First 2-fluorobenzonitrile reacts with the Grignard reagent cyclopentyl magnesium bromide followed by a bromination reaction to obtain α-bromocyclopentyl-(2-fluorophenyl)-ketone. The reaction of the obtained ketone with methylamine at −40 °C then results in the formation of α-hydroxycyclopentyl-(2-fluorophenyl)-N-methylamine. Finally, the five-membered ring cyclopentanol form is expanded to a cyclohexylketone form by a thermal rearrangement reaction. HCl is used to create a water-soluble HCl salt of 2-FDCK. Detection 2-FDCK and its metabolites can be detected in urine with the use of liquid chromatography mass spectrometry (LC/MS). Gicquel T, Pelletier R, Richeval C, Gish A, Hakim F, Ferron PJ, Mesli V, Allorge D, Morel I, Gaulier JM 6 Metabolite elucidation of 2-fluoro-deschloroketamine (2F-DCK) using molecular networking across three complementary in vitro and in vivo models Drug Testing and Analysis 14 1 144–153 January 2022 34515415 10.1002/dta.3162 237494122 https://hal.archives-ouvertes.fr/hal-03367830/file/Gicquel%20et%20al%20-%202021%20-%20Metabolite%20elucidation%20of%202-fluoro-deschloroketamine.pdf Pharmacology Metabolism class=skin-invert-image|thumb|335x335px|Multistep metabolism of 2-FDCK. The process starts at 2-FDCK itself, which is then converted to nor-2-FDCK. This compound can then undergo transformation to either dehydro-nor-2-FDCK or hydroxy-nor-2-FDCK. The metabolism of 2-FDCK is analogous to that of ketamine: the enzymes CYP2B6 and CYP3A4, the latter to a lesser extent, metabolise 2-FDCK to Nor-2FDCK via N-demethylation. This is further metabolised either to dehydronor-2FDCK by CYP2B6 or to hydroxynor-2FDCK by CYP2A6 and CYP2B6. In general, the 2-FDCK equivalent shows stronger docking to CYP2B6 in simulations, as well as slower metabolism rate, than the more well-known ketamine. The lipophilicity is observed to be lower for 2-FDCK than for ketamine. In vitro to in vivo extrapolation predicts that in the body, 2-FDCK shows a lower intrinsic hepatic clearance than ketamine. Both of these characteristics would suggest that the effects of 2-FDCK last longer than those of ketamine. Pharmacodynamics 2-FDCK is structurally similar to ketamine, so a similar mechanism of action is expected, Morris H, Wallach J From PCP to MXE: a comprehensive review of the non-medical use of dissociative drugs Drug Testing and Analysis 6 7–8 614–632 2014 24678061 10.1002/dta.1620 but there has been no study done to confirm this. Due to the halogen in the 2 position not being a chlorine but a fluorine, the molecule is more polar. This could influence binding to proteins, such as the NMDA receptor that ketamine primarily binds to and acts as an antagonist towards. Comparison to other halogen-substituted ketamine variants For general (halogen) substitutions of ketamine, docking strength for CYP2B6 follows the pattern H < Br < Cl < F. The parameter of internal clearance follows the pattern Br > Cl > F > H. Lastly, Km (Michaelis constant) follows the pattern of Br < Cl < F < H, and as such the in-vitro metabolism rate follows the inverse pattern, namely Br > Cl > F > H. Adverse effects Possible effects and dangers In 2019, 2-FDCK was found in poisoned individuals in Hong Kong in combination with other ketamine-type drugs. Legal status Due to the fast emergence of NPS, new substances such as 2-FDCK are often not yet specifically mentioned in controlled substance legislation. As a result, NPS are sometimes marketed as "legal highs". 2-FDCK is currently illegal in Italy Aggiornamento delle tabelle contenenti l'indicazione delle sostanze stupefacenti e psicotrope, di cui al decreto del Presidente della Repubblica 9 ottobre 1990, n. 309 e successive modificazioni ed integrazioni. Inserimento nella tabella I e nella tabella IV di nuove sostanze psicoattive https://www.gazzettaufficiale.it/eli/id/2020/03/30/20A01820/sg Article 1 13 March 2020 Italian Japan,"指定薬物一覧" (PDF) (in Japanese). Ministry of Health, Labour and Welfare Latvia, https://likumi.lv/doc.php?id=121086 Noteikumi par Latvijā kontrolējamajām narkotiskajām vielām, psihotropajām vielām un prekursoriem Latvian Latvijas Republikas tiesību akti Singapore, https://sso.agc.gov.sg/Act/MDA1973 Misuse of Drugs Act – Singapore Statutes Online sso.agc.gov.sg Sweden, Riksdagsförvaltningen https://www.riksdagen.se/sv/dokument-lagar/dokument/svensk-forfattningssamling/forordning-199958-om-forbud-mot-vissa_sfs-1999-58 Förordning (1999:58) om förbud mot vissa hälsofarliga varor Svensk författningssamling 1999:1999:58 t.o.m. SFS 2019:631 – Riksdagen www.riksdagen.se Swedish Switzerland, https://www.fedlex.admin.ch/eli/cc/2011/363/de Verordnung des EDI über die Verzeichnisse der Betäubungsmittel, psychotropen Stoffe, Vorläuferstoffe und Hilfschemikalien German Der Bundesrat as well as being covered by blanket bans in Canada, https://laws-lois.justice.gc.ca/eng/acts/C-38.8/ Controlled Drugs and Substances Act (S.C. 1996, c. 19) March 18, 2021 Belgium, de Schutter A, Evenepoel T, Schrooten J 2019 https://www.vad.be/assets/dossier-nieuwe-psychoactieve-stoffen Dossier Nieuwe Psychoactieve Stoffen Brussel VAD and the UK. https://www.legislation.gov.uk/ukpga/1971/38/schedule/2 Misuse of Drugs Act 1971 7 March 2021 In October 2023 the ECDD recommended that 2-FDCK be added to Schedule II of the Convention on Psychotropic Substances of 1971. https://www.unodc.org/LSS/Announcement/Details/93c6537d-52c7-49b8-aaf6-2673203de9cd World Health Organization recommends five NPS for scheduling 22 January 2024 As of February 2026 2F-DCK is banned in the Netherlands and not sold anymore by research chemical shops, being replaced by 2F-NENDCK.2026-02-02 New Arrivals 2026: DCK, 2F-NENDCK & 3D-MXE Pellets Now in Stock https://eurochems.net/out-with-the-old-in-with-the-bold-the-2026-eurochems-catalog-update/ 2026-02-11 en-US United States On January 20, 2026 the DEA announced a temporary order to add 2-FDCK to Schedule 1 under the Controlled Substances Act on or after February 19, 2026.2026-01-20 Schedules of Controlled Substances: Temporary Placement of 2-Fluorodeschloroketamine in Schedule I https://www.federalregister.gov/documents/2026/01/20/2026-00954/schedules-of-controlled-substances-temporary-placement-of-2-fluorodeschloroketamine-in-schedule-i 2026-01-20 Federal Register en See also List of investigational hallucinogens and entactogens 2F-NENDCK 2-FXPr 3-Fluorodeschloroketamine Blixeprodil Bromoketamine Deschloroketamine Fluorexetamine Methoxyketamine Trifluoromethyldeschloroketamine References Category:Arylcyclohexylamines Category:Designer drugs Category:Dissociative drugs Category:Experimental hallucinogens Category:2-Fluorophenyl compounds Category:Ketones Category:NMDA receptor antagonists Category:Secondary amines