Details
| Stereochemistry | ABSOLUTE |
| Molecular Formula | C24H37N3O2 |
| Molecular Weight | 399.5695 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 2 / 2 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CCN1C(=O)N([C@@H]2CCN(CC3CCCCCCC3)C[C@H]2CO)C4=CC=CC=C14
InChI
InChIKey=MBGVUMXBUGIIBQ-LEWJYISDSA-N
InChI=1S/C24H37N3O2/c1-2-26-22-12-8-9-13-23(22)27(24(26)29)21-14-15-25(17-20(21)18-28)16-19-10-6-4-3-5-7-11-19/h8-9,12-13,19-21,28H,2-7,10-11,14-18H2,1H3/t20-,21+/m0/s1
DescriptionCurator's Comment: Description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/10602690 | https://www.ncbi.nlm.nih.gov/pubmed/18759357 | https://www.ncbi.nlm.nih.gov/pubmed/17287504 | https://www.ncbi.nlm.nih.gov/pubmed/20950413
Curator's Comment: Description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/10602690 | https://www.ncbi.nlm.nih.gov/pubmed/18759357 | https://www.ncbi.nlm.nih.gov/pubmed/17287504 | https://www.ncbi.nlm.nih.gov/pubmed/20950413
J-113397 (ComB) is the first potent and selective small molecule ORL1 antagonist. Merck, in collaboration with Banyu, is developing J-113397 with potential use in the treatment of pain. Preclinical development is underway in Japan, however, no recent development has been reported. In addition to antinociceptive properties J-113397 exerts antiparkinsonian action in animal models.
Approval Year
PubMed
| Title | Date | PubMed |
|---|---|---|
| Discovery of the first potent and selective small molecule opioid receptor-like (ORL1) antagonist: 1-[(3R,4R)-1-cyclooctylmethyl-3- hydroxymethyl-4-piperidyl]-3-ethyl-1, 3-dihydro-2H-benzimidazol-2-one (J-113397). | 1999 Dec 16 |
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| In vitro and in vivo pharmacological characterization of J-113397, a potent and selective non-peptidyl ORL1 receptor antagonist. | 2000 Aug 18 |
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| Enhanced spinal nociceptin receptor expression develops morphine tolerance and dependence. | 2000 Oct 15 |
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| In vitro inhibitory effects of J-113397 on nociceptin/orphanin FQ-stimulated. | 2001 Jun 13 |
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| Antitussive action of nociceptin in the cat. | 2001 Oct 26 |
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| Gastric acid secretion stimulated by centrally injected nociceptin in urethane-anesthetized rats. | 2002 Apr 19 |
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| Antagonistic effects of CompB on orphanin FQ-induced colonic contractions in rats. | 2002 Nov 1 |
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| Blockade of nociceptin/orphanin FQ transmission attenuates symptoms and neurodegeneration associated with Parkinson's disease. | 2005 Oct 19 |
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| The nociceptin/orphanin FQ receptor antagonist J-113397 and L-DOPA additively attenuate experimental parkinsonism through overinhibition of the nigrothalamic pathway. | 2007 Feb 7 |
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| The anxiolytic-like effects of the novel, orally active nociceptin opioid receptor agonist 8-[bis(2-methylphenyl)methyl]-3-phenyl-8-azabicyclo[3.2.1]octan-3-ol (SCH 221510). | 2008 Aug |
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| 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. | 2008 Jan 15 |
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| Nociceptin/orphanin FQ receptor activation attenuates antinociception induced by mixed nociceptin/orphanin FQ/mu-opioid receptor agonists. | 2009 Dec |
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| Further evidence for an involvement of nociceptin/orphanin FQ in the pathophysiology of Parkinson's disease: a behavioral and neurochemical study in reserpinized mice. | 2010 Dec |
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| Dual motor response to l-dopa and nociceptin/orphanin FQ receptor antagonists in 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) treated mice: Paradoxical inhibition is relieved by D(2)/D(3) receptor blockade. | 2010 Jun |
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| Endogenous nociceptin/orphanin FQ (N/OFQ) contributes to haloperidol-induced changes of nigral amino acid transmission and parkinsonism: a combined microdialysis and behavioral study in naïve and nociceptin/orphanin FQ receptor knockout mice. | 2010 Mar 10 |
|
| Anti-inflammatory and antinociceptive action of an orally available nociceptin receptor agonist SCH 221510 in a mouse model of inflammatory bowel diseases. | 2014 Mar |
Patents
Sample Use Guides
3-30 mg/kg s.c. J-113397 dose-dependently antagonised the nociceptin-induced hyperalgesia in mouse/rat thermal pain models .
0.01-10 mg/kg i.p. J-113397 attenuated haloperidol-induced motor deficits.
Route of Administration:
Other
Under voltage-clamp conditions, bath application of N/OFQ (10 pM-1 microM) resulted in a dose-dependent depression of whole cell currents in neurons of diagonal band of Broca. J-113397 antagonized the N/OFQ response with an IC50value of 8.7 nM.
ORL1 antagonist J-113397 (1 microM) produced no change in membrane current in rat rostral ventromedial medulla (RVM) neurons and abolished the outward current produced by nociceptin (100 nM)
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5311194
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256640-45-6
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DTXSID801018432
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J-113,397
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00M5444DIY
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ACTIVE MOIETY
