217461-40-0

Usage

Uses

Used in Pharmaceutical Industry:
(±)-1-[(3R,4R)-1-(Cyclooctylmethyl)-3-(hydroxymethyl)-4-piperidinyl]-3-ethyl-1,3-dihydro-2H-benzimidazol-2-one is used as a potent nociceptin/orphanin FQ receptor antagonist for the development of novel therapeutics targeting the ORL-1 receptor. Its application reason is based on its ability to modulate the nociceptin/orphanin FQ receptor, which is involved in various physiological processes and has been implicated in pain transmission, stress response, and addiction.
Used in Pain Management:
In the field of pain management, (±)-1-[(3R,4R)-1-(Cyclooctylmethyl)-3-(hydroxymethyl)-4-piperidinyl]-3-ethyl-1,3-dihydro-2H-benzimidazol-2-one is used as a non-peptide ORL-1 receptor antagonist to help alleviate pain by blocking the nociceptin/orphanin FQ receptor. This application is due to the receptor's role in pain transmission, making it a potential target for the development of new pain relief medications.
Used in Addiction Treatment:
(±)-1-[(3R,4R)-1-(Cyclooctylmethyl)-3-(hydroxymethyl)-4-piperidinyl]-3-ethyl-1,3-dihydro-2H-benzimidazol-2-one is also used as a potential therapeutic agent in addiction treatment. Its application reason is based on the involvement of the nociceptin/orphanin FQ receptor in the regulation of stress response and reward pathways, which are often dysregulated in addiction.
Used in Stress Response Research:
In the field of stress response research, (±)-1-[(3R,4R)-1-(Cyclooctylmethyl)-3-(hydroxymethyl)-4-piperidinyl]-3-ethyl-1,3-dihydro-2H-benzimidazol-2-one is used as a research tool to better understand the role of the nociceptin/orphanin FQ receptor in stress response mechanisms. This application is important for developing new strategies to manage stress-related disorders and improve overall mental health.

Biological Activity

(±)-j 113397 is a potent and selective non-peptidyl antagonist of orl1 receptor, with a ki value of 1.8 nm for cloned human orl1 [1].the orl1 receptor is a g protein-coupled. it is structurally related to the opioid receptors. the heptadecapeptide nociceptin/orphanin fq is the endogenous ligand [2].in cho-orl1 cells, nociceptinr/orphanin fq dose-dependently suppressed the accumulation of cyclic amp stimulated by forskolin with an ec value of 0.22 ± 0.011 nm. treatment with j-113397 at increasing concentration shifted the concentration-response curve of nociceptinr/orphanin fq to the right. data indicated that j-113397 inhibited the interaction between nociceptinr/orphanin fq and orl1 in a competitive manner [1].in a tail-flick test, an i.c.v. injection of nociceptinr/orphanin fq at 0.01-1 nmol or saline was given to mice. i.c.v. injection of saline did not obviously change the latency of tail-flick. nociceptinr/orphanin fq at doses of more than 0.1 nmol shortened the latency. at the high concentration, the effect of nociceptinr/orphanin fq reached a maximal decrease at 15 min after the injection of j-113397. the effect of nociceptinr/orphanin fq lasted for more than 60 min. j-113397 inhibited the shortening of mouse tail-flick latency induced by nociceptinr/orphanin fq dose-dependently. j-113397 at 30 mg/kg completely reversed the hyperalgesia elicited by nociceptinr/orphanin fq [1].

references

[1]. ozaki s, kawamoto h, itoh y, et al. in vitro and in vivo pharmacological characterization of j-113397, a potent and selective non-peptidyl orl1 receptor antagonist. european journal of pharmacology, 2000, 402(1): 45-53.[2]. mollereau c, mouledous l. tissue distribution of the opioid receptor-like (orl1) receptor. peptides, 2000, 21(7): 907-917.

Upstream product

• 361343-44-4 1-(cyclooctylmethyl)-4-(2-oxo-2,3-dihydrobenzoimidazol-1-yl)-1,2,5,6-tetrahydropyridine-3-carboxylic acid methyl ester 
• 62034-88-2 cyclooctyl carboxaldehyde dimethyl acetal 
• 6688-11-5 cyclooctylcarboxaldehyde 
• 4644-61-5 ethyl 4-piperidone-3-carboxylate hydrochloride 
• 1041872-14-3 C₃₂H₅₀N₄O₅ 
• 361343-43-3 [1-(cyclooctylmethyl)-5-methoxycarbonyl-1,2,5,6-tetrahydropyridin-4-yl]-2-oxo-2,3-dihydrobenzoimidazole-1-carboxylic acid tert-butyl ester 
• 361343-45-5 1-(1-cycloctylmethyl-3-methoxycarbonyl-1,2,5,6-tetrahydro-pyridin-4-yl)-3-ethyl-1,3-dihydro-2H-benzimidazol-2-one 
• 361343-37-5 4-[(2-aminophenyl)amino]-1-(cyclooctylmethyl)-1,2,5,6-tetrahydropyridine-3-carboxylic acid methyl ester 
• 256640-47-8 ethyl 4-amino-1-cyclooctylmethyl-1,2,5,6-tetrahydro-3-pyridinecarboxylate 
• 217463-45-1 ethyl 1-cyclooctylmethyl-4-oxo-3-piperidinecarboxylate 
• 361343-41-1 methyl 3-[cycloctylmethyl-(2-methoxycarbonylethyl)amino]propanoate 
• 361343-38-6 1-cycloctylmethyl-3-methoxycarbonyl-piperidin-4-one 
• 361343-39-7 N-(cyclooct-1-enylmethyl)ethanamide 
• 361343-40-0 N-(cyclooctylmethyl)ethanamide 

Relevant academic research and scientific papers

Improved synthesis of the ORL antagonist 1-[(3R,4R)-1-cyclooctylmethyl-3- ethoxycarbonyl-4-piperidinyl]-3-ethyl-1,3-dihydro-2H-benzimidazol-2-one (J-113397)

A practical synthesis of optically pure 1-[(3R,4R)-1-cyclooctylmethyl-3- ethoxycarbonyl-4-piperidinyl]-3-ethyl-1,3-dihydro-2H-benzimidazol-2-one (J-113397) was developed that avoids the use of chiral columns. Copyright Taylor & Francis Group, LLC.

Identification of an achiral analogue of J-113397 as potent nociceptin/orphanin FQ receptor antagonist

To date, J-113397 represents the most potent and selective non peptide NOP receptor antagonist widely used in pharmacological studies. However, the synthesis, purification, and enantiomer separation of this molecule, which contains two chiral centers, is

Synthesis of J-113397, the first potent and selective ORL1 antagonist

The first potent and selective small molecule ORL1 antagonist 1-[(3R,4R)-1-cyclooctylmethyl-3-hydroxymethyl-4-piperidyl]-3-ethyl-1,3-dih ydro-2H-benzimidazol-2-one (J-113397) was synthesized. J-113397 is the only available potent and selective ORL1 antagonist, which is a very useful pharmacological tool for elucidating the physiological roles of the nociceptin-ORL1 system. J-113397 was synthesized from ethyl 4-oxo-3-piperidinecarboxylate and a coupling reaction of 2-fluorobenzene with 4-amino-ethoxycarbonylpiperidine is a key step.

Efficient and practical asymmetric synthesis of 1-tert-butyl 3-methyl (3R,4R)-4-(2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)piperidine-1,3-dicarboxylate, a useful intermediate for the synthesis of nociceptin antagonists

An efficient and practical asymmetric synthesis of 1-tert-butyl 3-methyl (3R,4R)-4-(2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)piperidine-1,3-dicarboxylate 1, a useful intermediate for the synthesis of nociceptin antagonists, has been developed. This method i

A new synthesis of the ORL-1 antagonist 1-[(3R,4R)-1-cyclooctylmethyl-3-hydroxymethyl-4-piperidinyl]-3-ethyl-1,3-dihydro-2H-benzimidazol-2-one (J-113397) and activity in a calcium mobilization assay

A new chiral synthesis of the ORL-1 antagonist 1-[(3R,4R)-1-cyclooctylmethyl-3-hydroxymethyl-4-piperidinyl]-3-ethyl-1,3-dihydro-2H-benzimidazol-2-one (2, J-113397) was developed. J-113397 has a Ke = 0.85 nM in an ORL-1 calcium mobilization assa

A new synthetic approach to 1-[(3R,4R)-1-cyclooctylmethyl-3-hydroxymethyl-4-piperidyl]-3-ethyl-1,3-dihydro-benzimidazol-2-one (J-113397), the first non-peptide ORL-1 receptor antagonist

An efficient approach to 1-[(3R,4R)-1-cyclooctylmethyl-3-hydroxymethyl-4-piperidyl]-3-ethyl-1,3-dihydro-benzimidazol-2-one (J-113397)1, the first non-peptide ORL-1 receptor antagonist described in literature, is outlined. After construction of the piperidine framework through Dieckmann cyclization of the Michael adduct 8 of cyclooctylmethylamine to methyl acrylate, condensation with o-phenylendiamine produced the β-enamino ester 2, which has been conveniently used to construct the benzimidazolone substituent at C-4. Catalytic hydrogenation of intermediate 11 followed by base-promoted cis-trans isomerization of the key compound 12 led to the formation of ester 13, which was converted to the racemic title compound by LiAlH4 reduction. The pure enantiomers were obtained by chiral preparative HPLC separation using a derivatized celllose-based stationary phase. Copyright

2-oxoimidazole derivatives

The present invention relates to a compound represented by Formula [I] wherein represents an aromatic carbo- or heterocyclic ring which may have a substituent; Cy represents a mono-, bi- or tricyclic aliphatic carbocyclic group having 3 to 20 carbon atoms, which may have a substituent; represents a mono- or bicyclic aliphatic nitrogen-containing heterocyclic group having 3 to 14 carbon atoms, which may have a substituent; R1represents a hydrogen atom, a lower alkenyl group, a lower alkynyl group, a cyclo(lower alkyl) group, an amino group, a lower alkylamino group, a di(lower alkyl)-amino group, a hydroxyl group, a lower alkoxy group, a carboxyl group, a lower alkoxycarbonyl group, a carbamoyl group, a lower alkylcarbamoyl group or a di(lower alkyl)carbamoyl group, or a lower alkyl group which may have a substituent; and R2represents a hydrogen atom or a lower alkyl group, a salt or ester thereof, a production process for the same, and an analgesic, a reliever against tolerance to a narcotic analgesic represented by morphine, a reliever against dependence on a narcotic analgesic represented by morphine, an analgesic enhancer, an antiobestic, a drug for ameliorating brain function, a remedy for schizophrenia, a remedy for Parkinsonism, a remedy for chorea, an antidepressant, a remedy for diabetes insipidus, a remedy for polyuria, or a remedy for hypotension, comprising an effective ingredient of the same.