J-113,397 is an

opioid Opioids are substances that act on opioid receptors to produce morphine-like effects. Medically they are primarily used for pain relief, including anesthesia. Other medical uses include suppression of diarrhea, replacement therapy for opioid use ...

drug which was the first compound found to be a highly selective antagonist for the

nociceptin receptor The nociceptin opioid peptide receptor (NOP), also known as the nociceptin/orphanin FQ (N/OFQ) receptor or kappa-type 3 opioid receptor, is a protein that in humans is encoded by the ''OPRL1'' (opioid receptor-like 1) gene. The nociceptin receptor ...

, also known as the ORL-1 receptor. It is several hundred times selective for the ORL-1 receptor over other opioid receptors, and its effects in animals include preventing the development of tolerance to

morphine Morphine is a strong opiate that is found naturally in opium, a dark brown resin in poppies (''Papaver somniferum''). It is mainly used as a pain medication, and is also commonly used recreationally, or to make other illicit opioids. T ...

, the prevention of

hyperalgesia Hyperalgesia ( or ; 'hyper' from Greek ὑπέρ (huper, “over”), '-algesia' from Greek algos, ἄλγος (pain)) is an abnormally increased sensitivity to pain, which may be caused by damage to nociceptors or peripheral nerves and can ...

induced by intracerebroventricular administration of nociceptin (orphanin FQ), as well as the stimulation of dopamine release in the striatum, which increases the rewarding effects of

cocaine Cocaine (from , from , ultimately from Quechua: ''kúka'') is a central nervous system (CNS) stimulant mainly used recreationally for its euphoric effects. It is primarily obtained from the leaves of two Coca species native to South Ameri ...

, but may have clinical application in the treatment of

Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms becom ...

Synthesis

Patents for treating arrhythmia:Guo Zheng, et al. & (2020). J-113,397 synthesis (2007)

Condensation between 1-Benzyl-3-methoxycarbonyl-4-piperidone 7611-47-9(1) and

O-Phenylenediamine ''o''-Phenylenediamine (OPD) is an organic compound with the formula C6H4(NH2)2. This aromatic diamine is an important precursor to many heterocyclic compounds. It is isomeric with ''m''-phenylenediamine and ''p''-phenylenediamine. Preparation ...

(2) give
CID:16726310
(3). Reaction with

boc anhydride Di-''tert''-butyl dicarbonate is a reagent widely used in organic synthesis. Since this compound can be regarded formally as the acid anhydride derived from a ''tert''-butoxycarbonyl (Boc) group, it is commonly referred to as Boc anhydride. This ...

followed by treatment with

trifluoroacetic acid Trifluoroacetic acid (TFA) is an organofluorine compound with the chemical formula CF3CO2H. It is a structural analogue of acetic acid with all three of the acetyl group's hydrogen atoms replaced by fluorine atoms and is a colorless liquid with ...

give
CID:16726358
(4). Reaction with

iodoethane Ethyl iodide (also iodoethane) is a colorless flammable chemical compound. It has the chemical formula C2H5I and is prepared by heating ethanol with iodine and phosphorus.''Merck Index of Chemicals and Drugs'', 9th ed., monograph 3753 On contact ...

in the presence of base alkylates the urea nitrogen givin
CID:16726359
(5). Reduction of the enamine by treatment with magnesium metal in methanol solvent occurs to give predominantly the trans isomer
CID:16726360
(6). Catalytic removal of the benzyl group give
CID:16726362
(7). Reductive amination with Cyclooctanecarbaldehyde 688-11-5(7) give
CID:16726364
(9). Lastly, reduction of the ester with lithium aluminium hydride completed the synthesis of J-113397 (10).

References

{{Opioidergics Synthetic opioids Benzimidazoles Piperidines Ureas Primary alcohols Nociceptin receptor antagonists

Synthesis

See also

References