Potency and safety analysis of hemp-derived delta-9 products: The hemp vs. cannabis demarcation problem

AP-238
Legal status
Legal status	UK: Under Psychoactive Substances Act; US: The DEA is not of the opinion that AP-237 and derivatives are Controlled Substances, or analogues thereof. ;
Identifiers
	IUPAC name 1-[(2R,6S)-2,6-dimethyl-4-[(E)-3-phenylprop-2-enyl]piperazin-1-yl]propan-1-one;
CAS Number	(racemic) 4204-01-7 (racemic) ; 140924-11-4 (2R,6S enantiomer);
PubChem CID	124389619;
ChemSpider	4941886;
UNII	N26WML8AR7;
Chemical and physical data
Formula	C18H26N2O
Molar mass	286.419 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CCC(=O)N1[C@@H](CN(C[C@@H]1C)C/C=C/C2=CC=CC=C2)C;
	InChI InChI=1S/C18H26N2O/c1-4-18(21)20-15(2)13-19(14-16(20)3)12-8-11-17-9-6-5-7-10-17/h5-11,15-16H,4,12-14H2,1-3H3/b11-8+/t15-,16+; Key:JELNWDOXWGBBLO-QJBCGIKSSA-N;

AP-238 is an opioid designer drug related to drugs such as azaprocin and bucinnazine, with around the same potency as morphine.^[2] It was first discovered in Italy in the 1960s but was never marketed,^[3] subsequently appearing on the illicit market around 2020 and being detected in both Slovenia and the USA.^[4]^[5]

References

^ "2-Methyl-AP-237" (PDF). Office of Diversion Control. U.S Drug Enforcement Administration.
^ Fogarty MF, Vandeputte MM, Krotulski AJ, Papsun D, Walton SE, Stove CP, Logan BK (June 2022). "Toxicological and pharmacological characterization of novel cinnamylpiperazine synthetic opioids in humans and in vitro including 2-methyl AP-237 and AP-238". Archives of Toxicology. 96 (6): 1701–1710. doi:10.1007/s00204-022-03257-7. PMID 35275255. S2CID 247383361.
^ Cignarella G, Testa E (May 1968). "2,6-Dialkylpiperazines. IV. 1-Propionyl-4-substituted cis-2,6-dimethylpiperazines structurally related to the analgetic 8-acyl-3,8-diazabicyclo[3.2.1]octanes". Journal of Medicinal Chemistry. 11 (3): 592–594. doi:10.1021/jm00309a039. PMID 5656502.
^ {{cite web | url = https://www.policija.si/apps/nfl_response_web/0_Analytical_Reports_final/AP-238-ID-2185-20_report.pdf | title = Analytical Report. AP-238. 1-{2,6‐dimethyl‐4‐[(2E)‐3‐phenylprop‐2‐en‐1‐yl]piperazin‐1‐yl}propan-1-one. | work =Nacionalni Forenzični Laboratorij | date = 20 October 2020 }}
^ "AP-238" (PDF). NPS Discovery at CFSRE. Center for Forensic Science Research and Education (CFSRE). 11 November 2020.

[1] "2-Methyl-AP-237" (PDF). Office of Diversion Control. U.S Drug Enforcement Administration.

[2] Fogarty MF, Vandeputte MM, Krotulski AJ, Papsun D, Walton SE, Stove CP, Logan BK (June 2022). "Toxicological and pharmacological characterization of novel cinnamylpiperazine synthetic opioids in humans and in vitro including 2-methyl AP-237 and AP-238". Archives of Toxicology. 96 (6): 1701–1710. doi:10.1007/s00204-022-03257-7. PMID 35275255. S2CID 247383361.

[3] Cignarella G, Testa E (May 1968). "2,6-Dialkylpiperazines. IV. 1-Propionyl-4-substituted cis-2,6-dimethylpiperazines structurally related to the analgetic 8-acyl-3,8-diazabicyclo[3.2.1]octanes". Journal of Medicinal Chemistry. 11 (3): 592–594. doi:10.1021/jm00309a039. PMID 5656502.

[4] {{cite web | url = https://www.policija.si/apps/nfl_response_web/0_Analytical_Reports_final/AP-238-ID-2185-20_report.pdf | title = Analytical Report. AP-238. 1-{2,6‐dimethyl‐4‐[(2E)‐3‐phenylprop‐2‐en‐1‐yl]piperazin‐1‐yl}propan-1-one. | work =Nacionalni Forenzični Laboratorij | date = 20 October 2020 }}

[5] "AP-238" (PDF). NPS Discovery at CFSRE. Center for Forensic Science Research and Education (CFSRE). 11 November 2020.

[1]

[2]

[3]

[4]

[5]

Piperazines
Simple piperazines (no additional rings)	Aminoethylpiperazine Diethylcarbamazine HEPPS Midafotel Piperazine PIPES
Phenylpiperazines	2C-B-PP 3,4-CFP Acaprazine Antrafenine Aripiprazole Batoprazine Bifeprunox BRL-15,572 Ciprofloxacin CSP-2503 Dapiprazole DCPP DMPP Diphenylpiperazine Dropropizine EGIS-12,233 Elopiprazole Eltoprazine Enpiprazole Ensaculin Etoperidone Flesinoxan Fluanisone Flibanserin Fluprazine Itraconazole Ketoconazole Levodropropizine Lorpiprazole mCPP Mefway MeOPP Mepiprazole Naftopidil Naluzotan Naphthylpiperazine Nefazodone Niaprazine Oxypertine Pardoprunox pCPP pFPP Posaconazole S-14,506 S-14,671 S-15,535 SB-258,585 SB-271,046 SB-357,134 SB-399,885 Sonepiprazole TFMPP Tolpiprazole Trazodone Urapidil Vesnarinone Vilazodone Vortioxetine WAY-100,135 WAY-100,635
Benzylpiperazines	2C-B-BZP 3-Methylbenzylpiperazine Befuraline Bifeprunox Buclizine BZP Chlorbenzoxamine DBZP Fipexide Imatinib MBZP MDBZP Meclozine Methoxypiperamide NSI-189 Piberaline Piribedil RN-1747 Sunifiram Trimetazidine Vesnarinone
Diphenylalkylpiperazines (benzhydrylalkylpiperazines)	AD-1211 Almitrine Amperozide BRL-15,572 Buclizine BW373U86 Cetirizine Chlorbenzoxamine Chlorcyclizine Cinnarizine Clocinizine Cyclizine DBL-583 Diphenpipenol Diphenylmethylpiperazine Dotarizine DPI-221 DPI-287 DPI-3290 GBR-12,783 GBR-12,935 GBR-13,069 GBR-13,098 GBR-13,119 Hydroxyzine JJC8-088 Lidoflazine Manidipine Meclozine MT-45 Oxatomide SNC-80 Vanoxerine
Pyrimidinylpiperazines	Buspirone Dasatinib Eptapirone Gepirone Ipsapirone Piribedil Pyrimidinylpiperazine Revospirone Tandospirone Tirilazad Trimazosin Umespirone Zalospirone
Pyridinylpiperazines	Atevirdine Azaperone Delavirdine Mirtazapine ORG-12962 Pyridinylpiperazine
Benzo(iso)thiazolyl piperazines	Lurasidone Perospirone Revospirone Tiospirone Ziprasidone
Tricyclics (piperazine attached via side chain)	Amoxapine Clopenthixol Clorotepine Clozapine Cyanothepin Doclothepin Docloxythepin Flupentixol Fluphenazine Isofloxythepin Loxapine Meperathiepin Metitepine Octomethothepin Olanzapine Opipramol Oxyclothepin Oxyprothepin Peradithiepin Perathiepin Perazine Perphenazine Pirenzepine Prochlorperazine Thiethylperazine Thiothixene Trifluoperazine Trifluthepin Zuclopenthixol
Others/Uncategorized	6-Nitroquipazine AP-238 Azimilide Bucinnazine Cinepazet Cinepazic acid Cinepazide CPD-1 Cyclohexylpiperazine EGIS-7625 Hexocyclium Indinavir JNJ-7777120 Lodenafil MK-212 Mirodenafil PB-28 Quipazine Ranolazine SA-4503 Sildenafil Tadalafil Vardenafil VUF-6002 WY-46824 Zipeprol

Legal status

Legal status	UK: Under Psychoactive Substances Act US: The DEA is not of the opinion that AP-237 and derivatives are Controlled Substances, or analogues thereof. ^[1]
Identifiers
IUPAC name 1-[(2R,6S)-2,6-dimethyl-4-[(E)-3-phenylprop-2-enyl]piperazin-1-yl]propan-1-one
CAS Number	(racemic) 4204-01-7 (racemic) 140924-11-4 (2R,6S enantiomer)
PubChem CID	124389619
ChemSpider	4941886
UNII	N26WML8AR7
Chemical and physical data
Formula	C₁₈H₂₆N₂O
Molar mass	286.419 g·mol⁻¹
3D model (JSmol)	Interactive image
SMILES CCC(=O)N1[C@@H](CN(C[C@@H]1C)C/C=C/C2=CC=CC=C2)C
InChI InChI=1S/C18H26N2O/c1-4-18(21)20-15(2)13-19(14-16(20)3)12-8-11-17-9-6-5-7-10-17/h5-11,15-16H,4,12-14H2,1-3H3/b11-8+/t15-,16+ Key:JELNWDOXWGBBLO-QJBCGIKSSA-N

Potency and safety analysis of hemp-derived delta-9 products: The hemp vs. cannabis demarcation problem

See also

References