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Details

Stereochemistry ACHIRAL
Molecular Formula C20H25ClN2O
Molecular Weight 344.878
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of JNJ-40411813

SMILES

CCCCN1C=CC(N2CCC(CC2)C3=CC=CC=C3)=C(Cl)C1=O

InChI

InChIKey=HYOGJHCDLQSAHX-UHFFFAOYSA-N
InChI=1S/C20H25ClN2O/c1-2-3-12-23-15-11-18(19(21)20(23)24)22-13-9-17(10-14-22)16-7-5-4-6-8-16/h4-8,11,15,17H,2-3,9-10,12-14H2,1H3

HIDE SMILES / InChI
Molecular Formula C20H25ClN2O
Molecular Weight 344.878
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/25032784 | https://www.ncbi.nlm.nih.gov/pubmed/25692015 | https://www.ncbi.nlm.nih.gov/pubmed/25692027

ADX-71149 (JNJ-40411813), a phenylpiperidine-substituted pyridone, is positive allosteric modulator (PAM) metabotropic glutamate type 2 (mGlu2) receptor activity. In fed rats, JNJ-40411813 was rapidly absorbed with an absolute oral bioavailability of 31%. ADX-71149 (JNJ-40411813) demonstrates antipsychotic activity in vivo rodents experiments. ADX-71149 (JNJ-40411813) is being jointly developed by Addex Therapeutics and Janssen Pharmaceuticals, a Johnson & Johnson company, for the treatment of epilepsy. Addex Therapeutics was also developing the candidate for schizophrenia, major depressive disorder and anxiety disorders. However, development in these indications has been discontinued.

CNS Activity

Originator

Approval Year

Unknown
149124
Targets

Targets

Primary TargetPharmacologyConditionPotency
Metabotropic glutamate receptor 2
24
Target ID: Q14416
Gene ID: 2912.0
Gene Symbol: GRM2
Target Organism: Homo sapiens (Human)
Positive Allosteric Modulator
186
 147.0 nM [EC50]
Positive Allosteric Modulator
186
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Phase II
1147
Unknown

Approved Use

Unknown
Primary
Phase II
1147
Unknown

Approved Use

Unknown
Palliative
Phase II
1147
Unknown

Approved Use

Unknown
Primary
Phase II
1147
Unknown

Approved Use

Unknown
Primary
Phase II
1147
Unknown

Approved Use

Unknown
Primary
Phase II
1147
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
789 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/25735992
100 mg 2 times / day multiple, oral
dose: 100 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
JNJ-40411813 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
1246 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/25735992
100 mg 2 times / day multiple, oral
dose: 100 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
JNJ-40411813 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE
food status: UNKNOWN
1750 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/25735992
225 mg 2 times / day multiple, oral
dose: 225 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
JNJ-40411813 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
6404 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/25735992
100 mg 2 times / day multiple, oral
dose: 100 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
JNJ-40411813 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
10150 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/25735992
100 mg 2 times / day multiple, oral
dose: 100 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
JNJ-40411813 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE
food status: UNKNOWN
16191 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/25735992
225 mg 2 times / day multiple, oral
dose: 225 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
JNJ-40411813 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
24.2 h
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/25735992
100 mg 2 times / day multiple, oral
dose: 100 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
JNJ-40411813 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
29.6 h
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/25735992
100 mg 2 times / day multiple, oral
dose: 100 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
JNJ-40411813 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE
food status: UNKNOWN
34.2 h
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/25735992
225 mg 2 times / day multiple, oral
dose: 225 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
JNJ-40411813 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG
substrate
1946

inhibitor
2252
inhibitor
2438
inhibitor
2507
inhibitor
2217

OverviewOther

Other InhibitorOther SubstrateOther Inducer
CYP1A2
2153

P-gp
1741

CYP2C19
2057
HLM
34
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
P-gp
1932
 inconclusive [IC50 12.9953 uM]
CYP1A2
2333
 no [IC50 >18 uM]
CYP2D6
2546
 no [IC50 >18 uM]
CYP3A4
2633
 no [IC50 >18 uM]
CYP2C9
2497
 yes [IC50 6 uM]
CYP2C19
2141
 yes [IC50 7 uM]
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
CYP3A4
1946
 major
HLM
34
 yes
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
hERG
2263
PubMed

PubMed

TitleDatePubMed
Efficacy and safety of an adjunctive mGlu2 receptor positive allosteric modulator to a SSRI/SNRI in anxious depression.
2016-06-03
Translational neurophysiological markers for activity of the metabotropic glutamate receptor (mGluR2) modulator JNJ-40411813: Sleep EEG correlates in rodents and healthy men.
2016-04
Preclinical evaluation of the antipsychotic potential of the mGlu2-positive allosteric modulator JNJ-40411813.
2015-03
Pharmacological and pharmacokinetic properties of JNJ-40411813, a positive allosteric modulator of the mGlu2 receptor.
2015-02
Discovery of 1-butyl-3-chloro-4-(4-phenyl-1-piperidinyl)-(1H)-pyridone (JNJ-40411813): a novel positive allosteric modulator of the metabotropic glutamate 2 receptor.
2014-08-14
Patents

Patents

9132122
1
9266834
1
WO2016092002A1
1

Sample Use Guides

In Vivo Use Guide
In study 1, healthy men received 50-, 100-, 150- or 225 mg and women received 100 mg JNJ-40411813 (n=6, each cohort) or placebo (n=2, each cohort) twice daily for seven days; smoking men (n=30) received placebo twice daily on days 1-7, 100 mg JNJ-40411813 (n=20) or placebo (n=10) on days 8-14.
Route of Administration: Oral
In Vitro Use Guide
JNJ-40411813 acts as a positive allosteric modulator (PAM) at the cloned mGlu2 receptor: EC50 = 147 ± 42 nmol/L in a [35S]GTPγS binding assay with human metabotropic glutamate type 2 (hmGlu2) CHO cells and EC50 = 64 ± 29 nmol/L in a Ca2+ mobilization assay with hmGlu2 Gα16 cotransfected HEK293 cells. [35S]GTPγS autoradiography on rat brain slices confirmed PAM activity of JNJ-40411813 on native mGlu2 receptor. JNJ-40411813 displaced [3H]JNJ-40068782 and [3H]JNJ-46281222 (mGlu2 receptor PAMs), while it failed to displace [3H]LY341495 (a competitive mGlu2/3 receptor antagonist).
Substance Class Chemical
Created
by admin
on Mon Mar 31 23:14:32 GMT 2025
Edited
by admin
on Mon Mar 31 23:14:32 GMT 2025
Record UNII
612BYT76F3
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ADX-71149
Preferred Name English
JNJ-40411813
Common Name English
2(1H)-PYRIDINONE, 1-BUTYL-3-CHLORO-4-(4-PHENYL-1-PIPERIDINYL)-
Systematic Name English
1'-BUTYL-3'-CHLORO-4-PHENYL-3,4,5,6-TETRAHYDRO-2H,1'H-(1,4')BIPYRIDINYL-2'-ONE
Systematic Name English
Code System Code Type Description
EPA CompTox
DTXSID601032323
Created by admin on Mon Mar 31 23:14:32 GMT 2025 , Edited by admin on Mon Mar 31 23:14:32 GMT 2025
PRIMARY
CLINICAL_TRIALS.GOV
JNJ-40411813
Created by admin on Mon Mar 31 23:14:32 GMT 2025 , Edited by admin on Mon Mar 31 23:14:32 GMT 2025
PRIMARY Official Title: A Multicenter, Double-Blind, Placebo-Controlled Study of JNJ-40411813 as Adjunctive Treatment to an Antidepressant in Adults With Major Depressive Disorder With Anxiety SymptomsPurpose: The purpose of this study is to evaluate the efficacy and overall safety and tolerability of treatment with adjunctive JNJ-40411813 compared to placebo in patients with MDD with anxiety symptoms being treated with an antidepressant.
PUBCHEM
25195461
Created by admin on Mon Mar 31 23:14:32 GMT 2025 , Edited by admin on Mon Mar 31 23:14:32 GMT 2025
PRIMARY
SMS_ID
300000046596
Created by admin on Mon Mar 31 23:14:32 GMT 2025 , Edited by admin on Mon Mar 31 23:14:32 GMT 2025
PRIMARY
FDA UNII
612BYT76F3
Created by admin on Mon Mar 31 23:14:32 GMT 2025 , Edited by admin on Mon Mar 31 23:14:32 GMT 2025
PRIMARY
WIKIPEDIA
ADX-71149
Created by admin on Mon Mar 31 23:14:32 GMT 2025 , Edited by admin on Mon Mar 31 23:14:32 GMT 2025
PRIMARY ADX-71149, also known as JNJ-4041183 and JNJ-mGluR2-PAM, is a selective positive allosteric modulator of the mGlu2 receptor. It is being studied by Addex Therapeutics and Janssen Pharmaceuticals for the treatment of schizophrenia. It was also researched by these companies for the treatment of anxious depression (major depressive disorder with anxiety symptoms), but although some efficacy was observed in clinical trials, it was not enough to warrant further development for this indication. As of 2015, ADX-71149 is in phase II clinical trials for schizophrenia.
DRUG BANK
DB12059
Created by admin on Mon Mar 31 23:14:32 GMT 2025 , Edited by admin on Mon Mar 31 23:14:32 GMT 2025
PRIMARY
CAS
1127498-03-6
Created by admin on Mon Mar 31 23:14:32 GMT 2025 , Edited by admin on Mon Mar 31 23:14:32 GMT 2025
PRIMARY
Related Record Type Details
METABOTROPIC GLUTAMATE RECEPTOR 2
TARGET->MODULATOR
The pharmacokinetics and effects of JNJ-40411813 on cognition and subjective awareness were evaluated. Plasma JNJ-40411813 exposure was dose-dependent, t max ranged from 3-4 h and t 1/2 19.4-34.2 h across the dose levels. JNJ-40411813 significantly (p=0.02) reduced continuity of attention score (150 mg dose) and ameliorated smoking withdrawal-induced changes in power of attention and quality of episodic memory versus placebo. A modest reduction in alertness was observed at 150-225 mg doses, JNJ-40411813 (500 mg) reduced S(+) ketamine-induced negative symptoms by approximately 43% and 30% in cohorts 1 and 3, respectively. JNJ-40411813 was generally well-tolerated.
ALLOSTERIC ACTIVATOR
Related Record Type Details
Structure of JNJ-40411813
ACTIVE MOIETY
Originator: Addex Pharmaceuticals; Developer: Janssen Pharmaceuticals; Class: Antidepressant, Antipsychotic, Anxiolytic, Small molecule; Mechanism of Action: Metabotropic glutamate receptor 2 modulators; Highest Development Phases: Phase II for Major depressive disorder, Schizophrenia; Phase I for Psychiatric disorders; Most Recent Events: 22 Apr 2016 Chemical structure information added, 29 Jul 2015 Phase-II development is ongoing as adjunctive therapy for schizophrenia and for anxiety in major depressive disorder, 01 Nov 2013 Janssen completes a phase II trial in Major Depressive Disorder (adjunctive treatment in patients with anxiety symptoms) in Bulgaria, Hungary, Moldova, Romania, Russia and Ukraine (NCT01582815)
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