Details
Stereochemistry | ACHIRAL |
Molecular Formula | C17H17F5N4.2ClH |
Molecular Weight | 445.258 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
Cl.Cl.FC1=CC=C(CN2CCC(CC2)NC3=NN=C(C=C3)C(F)(F)F)C=C1F
InChI
InChIKey=UOLHGUUKFNZTNS-UHFFFAOYSA-N
InChI=1S/C17H17F5N4.2ClH/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);2*1H
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/22995972Curator's Comment: description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/22490380
Sources: https://www.ncbi.nlm.nih.gov/pubmed/22995972
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.
CNS Activity
Originator
Sources: https://www.ncbi.nlm.nih.gov/pubmed/22773165
Curator's Comment: # Janssen Research and Development, Janssen Pharmaceutica
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL217 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21890591 |
158.0 nM [Ki] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
28.6 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22773165 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22773165 |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
127 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22773165 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22773165 |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
30.5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22773165 |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
7.9% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22773165 |
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
Title | Date | PubMed |
---|---|---|
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 |
|
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 |
|
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
Sample Use Guides
In Vivo Use Guide
Sources: https://clinicaltrials.gov/ct2/show/NCT01812642
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
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/22490380
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.
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ACTIVE MOIETY
SUBSTANCE RECORD