Morpheridine

Chemical compound

none

Legal statusLegal status

AU: S9 (Prohibited substance)
BR: Class A1 (Narcotic drugs)^[1]
CA: Schedule I
DE: Anlage I (Authorized scientific use only)
UK: Controlled Drug
US: Schedule I
UN: Psychotropic Schedule I

Identifiers

IUPAC name

ethyl 1-(2-morpholin-4-ylethyl)-4-phenyl-piperidine-4-carboxylate

CAS Number

469-81-8^Y

PubChem CID

61121

ChemSpider

55069^Y

UNII

1854GKB41Y

CompTox Dashboard (EPA)

DTXSID20196979

ECHA InfoCard100.006.749

Chemical and physical dataFormulaC₂₀H₃₀N₂O₃Molar mass346.471 g·mol⁻¹3D model (JSmol)

Interactive image

SMILES

O=C(OCC)C3(c1ccccc1)CCN(CCN2CCOCC2)CC3

InChI

InChI=1S/C20H30N2O3/c1-2-25-19(23)20(18-6-4-3-5-7-18)8-10-21(11-9-20)12-13-22-14-16-24-17-15-22/h3-7H,2,8-17H2,1H3^Y
Key:JDEDMCKQPKGSAX-UHFFFAOYSA-N^Y

(verify)

Morpheridine (Morpholinoethylnorpethidine)^[2] is a 4-phenylpiperidine derivative that is related to the clinically used opioid analgesic drug pethidine (meperidine). It is a strong analgesic with around 4 times the potency of pethidine,^[3] and unlike pethidine, does not cause convulsions, although it produces the standard opioid side effects such as sedation and respiratory depression.^[4]

Morpheridine is not currently used in medicine and is a Schedule I drug which is controlled under UN drug conventions.^[5]

Synthesis

The key intermediate, normeperidine, is obtained by a scheme closely akin to the parent molecule. Thus, alkylation of benzyl cyanide (1) with the tosyl analog of the bischloroethylamine (2) leads to the substituted piperidine (3). Basic hydrolysis serves to convert the nitrile to the acid (4). Treatment of this last with sulfuric acid in ethanol serves both to esterify the acid and to remove the tosyl group to yield the secondary amine (5).

Alkylation of that amine by means of N-(2-chloroethyl)morpholine gives morpheridine.^[7]

References

^ Anvisa (2023-03-31). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 2023-04-04). Archived from the original on 2023-08-03. Retrieved 2023-08-16.
^ US 2795581, Stern ES, Anderson RJ, "Piperidine Compounds and Their Production", issued 06/11/1957, assigned to J.F. McFarlan & Co
^ Holmes JM (February 1958). "Morpholinoethylnorpethidine hydrochloride in obstetrics". The Journal of Obstetrics and Gynaecology of the British Empire. 65 (1): 98–9. doi:10.1111/j.1471-0528.1958.tb06218.x. PMID 13514558. S2CID 1481693.
^ Green AF, Ward NB (March 1956). "Analgesic and other properties of morpholinoethylnorpethidine". British Journal of Pharmacology and Chemotherapy. 11 (1): 32–4. doi:10.1111/j.1476-5381.1956.tb01023.x. PMC 1509567. PMID 13304251.
^ "Single convention on drugs 1961".
^ Thorp RH, Walton E (May 1948). "Search for new analgesics; further homologues of pethidine and the pharmacology of these and other compounds". Journal of the Chemical Society. 2: 559–61. doi:10.1039/JR9480000559. PMID 18869425.
^ Anderson RJ, Frearson PM, Stern ES (1956). "788. Some new analogues of pethidine. Part I". Journal of the Chemical Society (Resumed): 4088. doi:10.1039/JR9560004088.

Analgesics (N02A, N02B)

Opioids

Opiates/opium	Codeine^# +aspirin +paracetamol Morphine^# (+naltrexone) Opium Laudanum Paregoric
Semisynthetic	Acetyldihydrocodeine Benzylmorphine Buprenorphine (+naloxone) Butorphanol Desomorphine Diamorphine (heroin) Dihydrocodeine (+paracetamol) Dihydromorphine Etorphine Ethylmorphine Hydrocodone (+paracetamol, +ibuprofen, +aspirin) Hydromorphinol Hydromorphone Levorphanol Metopon Nalbuphine Nicocodeine Nicodicodine Nicomorphine Oxycodone (+paracetamol, +aspirin, +ibuprofen, +naloxone, +naltrexone) Oxymorphone Papaveretum Thebacon
Synthetic	Alfentanil Alphaprodine Anileridine Bezitramide Carfentanil Dextromoramide Dextropropoxyphene Dezocine Dimenoxadol Dipipanone Ethoheptazine Fentanyl^# (+fluanisone) Ketobemidone Lofentanil Meptazinol Methadone^# NFEPP Norpipanone Oliceridine Pentazocine Pethidine (meperidine) Phenadoxone Phenazocine Phenoperidine Piminodine Piritramide Proheptazine Propiram Remifentanil Sufentanil Tapentadol Tilidine Tramadol (+celecoxib, +paracetamol) Viminol

Paracetamol-type

NSAIDs

Propionates	Benoxaprofen ^‡ Fenoprofen Flurbiprofen Ibuprofen^# (Dexibuprofen) (+paracetamol) Ketoprofen (Dexketoprofen) Loxoprofen Naproxen Oxaprozin Suprofen Tiaprofenic acid Zaltoprofen
Oxicams	Isoxicam Lornoxicam Meloxicam Piroxicam Tenoxicam
Acetates	Acemetacin Bromfenac Diclofenac Etodolac Indometacin (Indometacin farnesil) Ketorolac Sulindac Tolmetin Zomepirac ^‡
COX-2 inhibitors	Celecoxib (+tramadol) Etoricoxib Lumiracoxib ^‡ Parecoxib Rofecoxib ^‡ Valdecoxib ^‡
Fenamates	Flufenamic acid Meclofenamic acid Mefenamic acid Tolfenamic acid
Salicylates	Aspirin (acetylsalicylic acid)^# (+paracetamol/caffeine) Aloxiprin Benorylate Carbasalate calcium Choline salicylate Diflunisal Dipyrocetyl Ethenzamide Guacetisal Imidazole salicylate Magnesium salicylate Morpholine salicylate Potassium salicylate Salicin Salicylamide Salsalate Sodium salicylate Wintergreen (methyl salicylate)
Pyrazolones	Aminophenazone^‡ Ampyrone Metamizole (dipyrone) Nifenazone Phenazone Propyphenazone (+paracetamol/caffeine)
Others	Benzydamine Floctafenine Glafenine Nabumetone Nimesulide Proquazone

Cannabinoids

Ion channel
modulators

Calcium blockers	Alcohol (ethanol) Gabapentin Gabapentin enacarbil Leconotide Mirogabalin Pregabalin Ziconotide
Sodium blockers	Carbamazepine Lacosamide Local anesthetics (e.g., cocaine, lidocaine) Mexiletine Nefopam Tricyclic antidepressants (e.g., amitriptyline^#) Na_v1.7/1.8-selective: DSP-2230^§ Funapide^§ PF-05089771^§
Potassium openers	Flupirtine^‡