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Details

Stereochemistry ACHIRAL
Molecular Formula C20H23N3O2
Molecular Weight 337.4155
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of E-52862

SMILES

CC1=CC(OCCN2CCOCC2)=NN1C3=CC4=C(C=CC=C4)C=C3

InChI

InChIKey=DGPGXHRHNRYVDH-UHFFFAOYSA-N
InChI=1S/C20H23N3O2/c1-16-14-20(25-13-10-22-8-11-24-12-9-22)21-23(16)19-7-6-17-4-2-3-5-18(17)15-19/h2-7,14-15H,8-13H2,1H3

HIDE SMILES / InChI

Description
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/22784008 | https://www.ncbi.nlm.nih.gov/pubmed/22404321

E-52862, also known as sigma-1 receptor antagonist (API-001, S1RA) successfully completed Phase I clinical trials for the treatment of pain, showing good safety and tolerability, and a pharmacokinetic profile compatible with once a day oral administration.

CNS Activity

Originator

Approval Year

Unknown
139594
Targets

Targets

Primary TargetPharmacologyConditionPotency
Sigma non-opioid intracellular receptor 1
26
Target ID: Q99720|||Q7Z653
Gene ID: 10280.0
Gene Symbol: SIGMAR1
Target Organism: Homo sapiens (Human)
Antagonist
2778
 17.0 nM [Ki]
Antagonist
2778
 17.0 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Phase I
428
Unknown

Approved Use

Unknown
Primary
Phase II
1132
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
5580.1 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/26291080
800 mg single, oral
dose: 800 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
E-52862 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
155911 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/26291080
800 mg single, oral
dose: 800 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
E-52862 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
41.5 h
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/26291080
800 mg single, oral
dose: 800 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
E-52862 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
Doses

Doses

DosePopulationAdverse events​
400 mg 1 times / day multiple, oral
Highest studied dose
Dose: 400 mg, 1 times / day
Route: oral
Route: multiple
Dose: 400 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/22607269/
healthy
n = 8
Health Status: healthy
Sex: M+F
Food Status: FASTED
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/22607269/
Sources:
https://pubmed.ncbi.nlm.nih.gov/22607269/
800 mg single, oral (unknown)
Highest studied dose
Dose: 800 mg
Route: oral
Route: single
Dose: 800 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/22607269/
healthy
n = 31
Health Status: healthy
Sex: M+F
Food Status: FASTED
Population Size: 31
Sources:
https://pubmed.ncbi.nlm.nih.gov/22607269/
Other AEs: Dissociation, Euphoric mood...
Other AEs:
Dissociation (6.5%)
Euphoric mood (6.5%)
Dizziness (19.4%)
headache (19.4%)
Nausea (12.9%)
Abnormal thinking (9.7%)
Euphoric mood (3.2%)
Palpitations (3.2%)
Sinus tachycardia (6.5%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/22607269/
AEs

AEs

AESignificanceDosePopulation
Nausea 12.9%
800 mg single, oral (unknown)
Highest studied dose
Dose: 800 mg
Route: oral
Route: single
Dose: 800 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/22607269/
healthy
n = 31
Health Status: healthy
Sex: M+F
Food Status: FASTED
Population Size: 31
Sources:
https://pubmed.ncbi.nlm.nih.gov/22607269/
Dizziness 19.4%
800 mg single, oral (unknown)
Highest studied dose
Dose: 800 mg
Route: oral
Route: single
Dose: 800 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/22607269/
healthy
n = 31
Health Status: healthy
Sex: M+F
Food Status: FASTED
Population Size: 31
Sources:
https://pubmed.ncbi.nlm.nih.gov/22607269/
headache 19.4%
800 mg single, oral (unknown)
Highest studied dose
Dose: 800 mg
Route: oral
Route: single
Dose: 800 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/22607269/
healthy
n = 31
Health Status: healthy
Sex: M+F
Food Status: FASTED
Population Size: 31
Sources:
https://pubmed.ncbi.nlm.nih.gov/22607269/
Euphoric mood 3.2%
800 mg single, oral (unknown)
Highest studied dose
Dose: 800 mg
Route: oral
Route: single
Dose: 800 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/22607269/
healthy
n = 31
Health Status: healthy
Sex: M+F
Food Status: FASTED
Population Size: 31
Sources:
https://pubmed.ncbi.nlm.nih.gov/22607269/
Palpitations 3.2%
800 mg single, oral (unknown)
Highest studied dose
Dose: 800 mg
Route: oral
Route: single
Dose: 800 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/22607269/
healthy
n = 31
Health Status: healthy
Sex: M+F
Food Status: FASTED
Population Size: 31
Sources:
https://pubmed.ncbi.nlm.nih.gov/22607269/
Dissociation 6.5%
800 mg single, oral (unknown)
Highest studied dose
Dose: 800 mg
Route: oral
Route: single
Dose: 800 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/22607269/
healthy
n = 31
Health Status: healthy
Sex: M+F
Food Status: FASTED
Population Size: 31
Sources:
https://pubmed.ncbi.nlm.nih.gov/22607269/
Euphoric mood 6.5%
800 mg single, oral (unknown)
Highest studied dose
Dose: 800 mg
Route: oral
Route: single
Dose: 800 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/22607269/
healthy
n = 31
Health Status: healthy
Sex: M+F
Food Status: FASTED
Population Size: 31
Sources:
https://pubmed.ncbi.nlm.nih.gov/22607269/
Sinus tachycardia 6.5%
800 mg single, oral (unknown)
Highest studied dose
Dose: 800 mg
Route: oral
Route: single
Dose: 800 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/22607269/
healthy
n = 31
Health Status: healthy
Sex: M+F
Food Status: FASTED
Population Size: 31
Sources:
https://pubmed.ncbi.nlm.nih.gov/22607269/
Abnormal thinking 9.7%
800 mg single, oral (unknown)
Highest studied dose
Dose: 800 mg
Route: oral
Route: single
Dose: 800 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/22607269/
healthy
n = 31
Health Status: healthy
Sex: M+F
Food Status: FASTED
Population Size: 31
Sources:
https://pubmed.ncbi.nlm.nih.gov/22607269/
PubMed

PubMed

TitleDatePubMed
Pharmacological properties of S1RA, a new sigma-1 receptor antagonist that inhibits neuropathic pain and activity-induced spinal sensitization.
2012 Aug
Synthesis and biological evaluation of the 1-arylpyrazole class of σ(1) receptor antagonists: identification of 4-{2-[5-methyl-1-(naphthalen-2-yl)-1H-pyrazol-3-yloxy]ethyl}morpholine (S1RA, E-52862).
2012 Oct 11
Safety, tolerability and pharmacokinetics of single and multiple doses of a novel sigma-1 receptor antagonist in three randomized phase I studies.
2013 Jan
Effects of the selective sigma-1 receptor antagonist S1RA on formalin-induced pain behavior and neurotransmitter release in the spinal cord in rats.
2014 May
The selective sigma-1 receptor antagonist E-52862 attenuates neuropathic pain of different aetiology in rats.
2016 Apr 18
Patents

Patents

WO2016138135A1
2

Sample Use Guides

In Vivo Use Guide
In a phase II study, treatment with single 400 mg dose of E 52862 before hysterectomy showed a clinically relevant reduction in pain intensity up to 24 hours post-surgery and a meaningful reduction for the need of concomitant anti-emetic medication in patients undergoing abdominal hysterectomy.
Route of Administration: Oral
In Vitro Use Guide
30 uM S1RA (E-52862) inhibited the spinal nociceptive C-fibre–dependent wind-up phenom-enon found when trains of stimuli were applied
Name Type Language
E-52862
Common Name English
S1RA
Common Name English
4-(2-(5-METHYL-1-(NAPHTHALEN-2-YL)-1H-PYRAZOL-3-YLOXY) ETHYL) MORPHOLINE
Systematic Name English
API-001
Code English
MORPHOLINE, 4-(2-((5-METHYL-1-(2-NAPHTHALENYL)-1H-PYRAZOL-3-YL)OXY)ETHYL)-
Systematic Name English
Code System Code Type Description
WIKIPEDIA
S1RA
Created by admin on Sat Dec 16 10:40:20 GMT 2023 , Edited by admin on Sat Dec 16 10:40:20 GMT 2023
PRIMARY S1RA, E-52862, or 4-(2-((5-methyl-1-(naphthalen-2-yl)-1H-pyrazol-3-yl)oxy)ethyl)morpholine is a selective sigma-1 receptor antagonist, with a reported binding affinity of Ki = 17.0 +/- 7.0 nM, selective over the sigma-2 receptor and against a panel of other 170 receptors, enzymes, transporters and ion channels.(1)(2) In preclinical studies, S1RA has demonstrated efficacy in relieving neuropathic pain and pain in other sensitizing conditions, associated with an improvement of the emotional negative state.S1RA is being developed by Esteve for the treatment of neuropathic pain and the potentiation of opioid analgesia and has successfully completed Phase I clinical trials showing good safety and tolerability, and a pharmacokinetic profile compatible with once a day oral administration. Phase II clinical trials are currently underway, making S1RA the first selective sigma-1 receptor antagonist evaluated in humans for these conditions.
CAS
878141-96-9
Created by admin on Sat Dec 16 10:40:20 GMT 2023 , Edited by admin on Sat Dec 16 10:40:20 GMT 2023
PRIMARY
SMS_ID
100000175800
Created by admin on Sat Dec 16 10:40:20 GMT 2023 , Edited by admin on Sat Dec 16 10:40:20 GMT 2023
PRIMARY
FDA UNII
ZW18DSD1H4
Created by admin on Sat Dec 16 10:40:20 GMT 2023 , Edited by admin on Sat Dec 16 10:40:20 GMT 2023
PRIMARY
EPA CompTox
DTXSID90102252
Created by admin on Sat Dec 16 10:40:20 GMT 2023 , Edited by admin on Sat Dec 16 10:40:20 GMT 2023
PRIMARY
PUBCHEM
44247568
Created by admin on Sat Dec 16 10:40:20 GMT 2023 , Edited by admin on Sat Dec 16 10:40:20 GMT 2023
PRIMARY
ACTIVE MOIETY
Structure of E-52862
SALT/SOLVATE (PARENT)
Structure of E-52862 HYDROCHLORIDE
NIH
NCATS
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