J-113397

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

Structure Search

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

HIDE SMILES / InChI

Molecular Formula	C24H37N3O2
Molecular Weight	399.5695
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: http://adisinsight.springer.com/drugs/800013348
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.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Nociceptin receptor 14 Target ID: CHEMBL2014 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10602690	Antagonist 2778		2.3 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Pain 614 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22120202 https://www.ncbi.nlm.nih.gov/pubmed/10940356	Primary		Basic research	Unknown Approved Use Unknown
Parkinson's disease 226 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18759357 https://www.ncbi.nlm.nih.gov/pubmed/17287504 https://www.ncbi.nlm.nih.gov/pubmed/20950413	Primary		Basic research	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Inhibitory activity of nociceptin/orphanin FQ on capsaicin-induced bronchoconstriction in the guinea-pig.	2001 Jul 27	11508352
In vitro inhibitory effects of J-113397 on nociceptin/orphanin FQ-stimulated.	2001 Jun 13	11409754
Antitussive action of nociceptin in the cat.	2001 Oct 26	11698070
Nociceptin inhibits excitatory but not inhibitory transmission to substantia gelatinosa neurones of adult rat spinal cord.	2002	11801370
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	17976996
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	20950413
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	20122926
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	20006677
Anti-inflammatory and antinociceptive action of an orally available nociceptin receptor agonist SCH 221510 in a mouse model of inflammatory bowel diseases.	2014 Mar	24345466

Patents

Sample Use Guides

In Vivo Use Guide

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

In Vitro Use Guide

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)

Substance Class	Chemical Created by `admin` on `Sat Dec 16 10:08:54 GMT 2023` Edited by `admin` on `Sat Dec 16 10:08:54 GMT 2023`
Record UNII	00M5444DIY
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

J-113397

Common Name

English

2H-BENZIMIDAZOL-2-ONE, 1-((3R,4R)-1-(CYCLOOCTYLMETHYL)-3-(HYDROXYMETHYL)-4-PIPERIDINYL)-3-ETHYL-1,3-DIHYDRO-

Systematic Name

English

COMPB

Common Name

English

J-113,397

Code

English

(+)-J-113397

Common Name

English

Code System Code Type Description

PUBCHEM

5311194