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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
Molecular Formula C20H23N3O2
Molecular Weight 337.4155
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

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

4-{2-[5-methyl-1-(naphthalen-2-yl)-1H-pyrazol-3-yloxy]ethyl}morpholine (S1RA, E-52862) is an 1-arylpyrazole class of sigma-1 receptor antagonist. Formalin-induced nociception (both phases), capsaicin-induced mechanical hypersensitivity and sciatic nerve injury-induced mechanical and thermal hypersensitivity were dose-dependently inhibited by systemic administration of S1RA. Occupancy of sigma-1 receptors in the CNS was significantly correlated with the antinociceptive effects. As a mechanistic correlate, electrophysiological recordings demonstrated that pharmacological antagonism of sigma-1 receptors attenuated the wind-up responses in spinal cords sensitized by repetitive nociceptive stimulation. Esteve is developing E 52862 for the treatment of several pain indications, including diabetic neuropathies, chemotherapy-induced neuropathic pain, postherpetic neuralgia, postoperative pain. Phase II development of this first-in-class agent is underway in Romania, Spain and Greece.

CNS Activity

Originator

Approval Year

Unknown
149124
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
2849
 17.0 nM [Ki]
Antagonist
2849
 17.0 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Phase I
438
Unknown

Approved Use

Unknown
Primary
Phase II
1147
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
Health Status: healthy
Sex: M+F
Food Status: FASTED
Sources:
https://pubmed.ncbi.nlm.nih.gov/22607269/
Sources:
https://pubmed.ncbi.nlm.nih.gov/22607269/
800 mg single, oral
Highest studied dose
Dose: 800 mg
Route: oral
Route: single
Dose: 800 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/22607269/
healthy
Health Status: healthy
Sex: M+F
Food Status: FASTED
Sources:
https://pubmed.ncbi.nlm.nih.gov/22607269/
Other AEs: headache, Dizziness...
Other AEs:
headache (19.4%)
Dizziness (19.4%)
Abnormal thinking (9.7%)
Dissociation (6.5%)
Euphoric mood (6.5%)
Euphoric mood (3.2%)
Nausea (12.9%)
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
Highest studied dose
Dose: 800 mg
Route: oral
Route: single
Dose: 800 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/22607269/
healthy
Health Status: healthy
Sex: M+F
Food Status: FASTED
Sources:
https://pubmed.ncbi.nlm.nih.gov/22607269/
Dizziness 19.4%
800 mg single, oral
Highest studied dose
Dose: 800 mg
Route: oral
Route: single
Dose: 800 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/22607269/
healthy
Health Status: healthy
Sex: M+F
Food Status: FASTED
Sources:
https://pubmed.ncbi.nlm.nih.gov/22607269/
headache 19.4%
800 mg single, oral
Highest studied dose
Dose: 800 mg
Route: oral
Route: single
Dose: 800 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/22607269/
healthy
Health Status: healthy
Sex: M+F
Food Status: FASTED
Sources:
https://pubmed.ncbi.nlm.nih.gov/22607269/
Euphoric mood 3.2%
800 mg single, oral
Highest studied dose
Dose: 800 mg
Route: oral
Route: single
Dose: 800 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/22607269/
healthy
Health Status: healthy
Sex: M+F
Food Status: FASTED
Sources:
https://pubmed.ncbi.nlm.nih.gov/22607269/
Palpitations 3.2%
800 mg single, oral
Highest studied dose
Dose: 800 mg
Route: oral
Route: single
Dose: 800 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/22607269/
healthy
Health Status: healthy
Sex: M+F
Food Status: FASTED
Sources:
https://pubmed.ncbi.nlm.nih.gov/22607269/
Dissociation 6.5%
800 mg single, oral
Highest studied dose
Dose: 800 mg
Route: oral
Route: single
Dose: 800 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/22607269/
healthy
Health Status: healthy
Sex: M+F
Food Status: FASTED
Sources:
https://pubmed.ncbi.nlm.nih.gov/22607269/
Euphoric mood 6.5%
800 mg single, oral
Highest studied dose
Dose: 800 mg
Route: oral
Route: single
Dose: 800 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/22607269/
healthy
Health Status: healthy
Sex: M+F
Food Status: FASTED
Sources:
https://pubmed.ncbi.nlm.nih.gov/22607269/
Sinus tachycardia 6.5%
800 mg single, oral
Highest studied dose
Dose: 800 mg
Route: oral
Route: single
Dose: 800 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/22607269/
healthy
Health Status: healthy
Sex: M+F
Food Status: FASTED
Sources:
https://pubmed.ncbi.nlm.nih.gov/22607269/
Abnormal thinking 9.7%
800 mg single, oral
Highest studied dose
Dose: 800 mg
Route: oral
Route: single
Dose: 800 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/22607269/
healthy
Health Status: healthy
Sex: M+F
Food Status: FASTED
Sources:
https://pubmed.ncbi.nlm.nih.gov/22607269/
PubMed

PubMed

TitleDatePubMed
The selective sigma-1 receptor antagonist E-52862 attenuates neuropathic pain of different aetiology in rats.
2016-04-18
Effects of the selective sigma-1 receptor antagonist S1RA on formalin-induced pain behavior and neurotransmitter release in the spinal cord in rats.
2014-05
Safety, tolerability and pharmacokinetics of single and multiple doses of a novel sigma-1 receptor antagonist in three randomized phase I studies.
2013-01
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).
2012-10-11
Pharmacological properties of S1RA, a new sigma-1 receptor antagonist that inhibits neuropathic pain and activity-induced spinal sensitization.
2012-08
Patents

Patents

WO2016138135A1
2

Sample Use Guides

In Vivo Use Guide
Three randomized, double-blind, placebo-controlled trials evaluated single oral doses (5-500 mg, study 101; 500-800 mg, study 106) and multiple doses (50-400 mg once daily for 8 days, study 102) of S1RA (API-001)
Route of Administration: Oral
In Vitro Use Guide
E-52862 (API-001) is a selective sigma-1 receptor (σ1R) antagonist, with 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. Binding affinity was performed to human σ1R transfected HEK-293 membranes using [3H](+)-pentazocine as radioligand.
Substance Class Chemical
Created
by admin
on Mon Mar 31 23:22:54 GMT 2025
Edited
by admin
on Mon Mar 31 23:22:54 GMT 2025
Record UNII
ZW18DSD1H4
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
E-52862
Common Name English
API-001
Preferred Name English
S1RA
Common Name English
4-(2-(5-METHYL-1-(NAPHTHALEN-2-YL)-1H-PYRAZOL-3-YLOXY) ETHYL) MORPHOLINE
Systematic Name 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 Mon Mar 31 23:22:54 GMT 2025 , Edited by admin on Mon Mar 31 23:22:54 GMT 2025
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 Mon Mar 31 23:22:54 GMT 2025 , Edited by admin on Mon Mar 31 23:22:54 GMT 2025
PRIMARY
SMS_ID
100000175800
Created by admin on Mon Mar 31 23:22:54 GMT 2025 , Edited by admin on Mon Mar 31 23:22:54 GMT 2025
PRIMARY
FDA UNII
ZW18DSD1H4
Created by admin on Mon Mar 31 23:22:54 GMT 2025 , Edited by admin on Mon Mar 31 23:22:54 GMT 2025
PRIMARY
EPA CompTox
DTXSID901022521
Created by admin on Mon Mar 31 23:22:54 GMT 2025 , Edited by admin on Mon Mar 31 23:22:54 GMT 2025
PRIMARY
PUBCHEM
44247568
Created by admin on Mon Mar 31 23:22:54 GMT 2025 , Edited by admin on Mon Mar 31 23:22:54 GMT 2025
PRIMARY
Related Record Type Details
Structure of E-52862 HYDROCHLORIDE
SALT/SOLVATE -> PARENT
SIGMA NON-OPIOID INTRACELLULAR RECEPTOR 1
TARGET -> INHIBITOR
Ki
Related Record Type Details
Structure of E-52862
ACTIVE MOIETY
Active Indications (Highest Phase): Phase II for Diabetic neuropathies, Neuropathic pain, Postherpetic neuralgia, Postoperative pain No Inactive Indications
NIH
NCATS
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