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Details

Stereochemistry ACHIRAL
Molecular Formula C17H17F5N4.ClH
Molecular Weight 408.797
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of JNJ-37822681 MONOHYDROCHLORIDE

SMILES

Cl.FC1=CC=C(CN2CCC(CC2)NC3=NN=C(C=C3)C(F)(F)F)C=C1F

InChI

InChIKey=LNROCDCNMOIIKD-UHFFFAOYSA-N
InChI=1S/C17H17F5N4.ClH/c18-13-2-1-11(9-14(13)19)10-26-7-5-12(6-8-26)23-16-4-3-15(24-25-16)17(20,21)22;/h1-4,9,12H,5-8,10H2,(H,23,25);1H

HIDE SMILES / InChI

Description
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/22490380

JNJ-37822681 is a novel, potent, specific, centrally active, dopamine D2 receptor antagonist, which was developed by Johnson & Johnson. This drug is in the phase II of clinical trial for the treatment of schizophrenia. JNJ-37822681 has optimal brain disposition and somnolence was the most frequently reported adverse effect.

Originator

Curator's Comment: # Janssen Research and Development, Janssen Pharmaceutica

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
158.0 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
28.6 ng/mL
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
JNJ-37822681 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
47.3 ng/mL
10 mg 2 times / day multiple, oral
dose: 10 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
JNJ-37822681 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
127 ng × h/mL
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
JNJ-37822681 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
341 ng × h/mL
10 mg 2 times / day multiple, oral
dose: 10 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
JNJ-37822681 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
30.5 h
10 mg 2 times / day multiple, oral
dose: 10 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
JNJ-37822681 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
7.9%
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
JNJ-37822681 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
PubMed

PubMed

TitleDatePubMed
Pharmacokinetics and central nervous system effects of the novel dopamine D2 receptor antagonist JNJ-37822681.
2012 Aug
In vivo quantification of striatal dopamine D2 receptor occupancy by JNJ-37822681 using [11C]raclopride and positron emission tomography.
2012 Aug
D₂-receptor occupancy measurement of JNJ-37822681, a novel fast off-rate D₂-receptor antagonist, in healthy subjects using positron emission tomography: single dose versus steady state and dose selection.
2012 Dec
A double-blind, randomized, placebo-controlled study with JNJ-37822681, a novel, highly selective, fast dissociating D₂ receptor antagonist in the treatment of acute exacerbation of schizophrenia.
2012 Oct
Metabolic and body mass parameters after treatment with JNJ-37822681, a novel fast-dissociating D2 receptor antagonist, vs olanzapine in patients with schizophrenia.
2013 Aug
Population pharmacokinetics of JNJ-37822681, a selective fast-dissociating dopamine D₂-receptor antagonist, in healthy subjects and subjects with schizophrenia and dose selection based on simulated D₂-receptor occupancy.
2013 Nov
Patents

Patents

Sample Use Guides

JNJ-37822681 oral capsule will be administered at a starting dose of 10 milligram (mg) twice daily for the first 3 days and thereafter dose will be titrated from Day 3 to Day 10 up to 80 mg per day and will be continued at same dose up to Day 14.
Route of Administration: Oral
Binding assays were carried out under incubation conditions. JNJ-37822681 was tested at a concentration of 1 μM by CEREP (Celle L'Evescault, France) for its inhibition of radioligand binding to a battery of other neurotransmitter receptors, peptide receptors, and neurotransmitter transporters. JNJ-37822681 had a moderate binding affinity for the dopamine D2L receptor (Ki 158 nM), similar to olanzapine and clozapine. JNJ-37822681 displayed a weak affinity for the human dopamine D3 and serotonin 5-HT2A receptors and did not interact with the human receptors dopamine D1, adrenergic α1A, serotonin 5-HT2C, and histamine H1, up to the highest (10 μM) concentration tested. Further profiling at CEREP did not reveal any additional interactions except a high affinity to σ1 receptors (Ki 8.9 nM). Overall, JNJ-37822681 shows a high D2 specificity, especially compared with the second-generation antipsychotics that display a moderate to weak affinity for the D2 receptor, such as olanzapine, clozapine, and quetiapine.
Name Type Language
JNJ-37822681 MONOHYDROCHLORIDE
Code English
Code System Code Type Description
PUBCHEM
131634970
Created by admin on Sat Dec 16 10:45:46 GMT 2023 , Edited by admin on Sat Dec 16 10:45:46 GMT 2023
PRIMARY
FDA UNII
7O420XPD11
Created by admin on Sat Dec 16 10:45:46 GMT 2023 , Edited by admin on Sat Dec 16 10:45:46 GMT 2023
PRIMARY