Compounds > rg 1678
Page last updated: 2024-08-03 11:25:42

rg 1678

Description

(4-(3-fluoro-5-trifluoromethylpyridin-2-yl)piperazin-1-yl)(5-methanesulfonyl-2-(2,2,2-trifluoro-1-methylethoxy)phenyl)methanone: a GlyT1 inhibitor; structure in first source [MeSH]

Cross-References

ID SourceID
PubMed CID24946690
CHEMBL ID1171829
SCHEMBL ID562490
MeSH IDM0547988

Synonyms (57)

Synonym
r-1678
bitopertin
rg-1678
paliflutine
ro-4917838
bdbm50322423
(s)-4-(3-fluoro-5-trifluoromethylpyridin-2-yl)piperazin-1-yl]-[5-methanesulfonyl-2-(2,2,2-trifluoro-1-methylethoxy)phenyl]-methanone
CHEMBL1171829 ,
ro4917838
ro-4917939
845614-11-1
piperazine, 1-(3-fluoro-5-(trifluoromethyl)-2-pyridinyl)-4-(5-(methylsulfonyl)-2-((1s)-2,2,2-trifluoro-1-methylethoxy)benzoyl)-
r 1678
(4-(3-fluoro-5-trifluoromethylpyridin-2-yl)piperazin-1-yl)(5-methylsulfonyl-2-(((s)-2,2,2-trifluoro-1-methylethyl)oxy)phenyl)methanone
methanone, (4-(3-fluoro-5-(trifluoromethyl)-2-pyridinyl)-1-piperazinyl)(5-(methylsulfonyl)-2-((1s)-2,2,2-trifluoro-1-methylethoxy)phenyl)-palmitoyl oligopeptide
q8l6an59yy ,
ro 4917939
rg 1678
ro 4917838
paliflutine [inn]
(4-(3-fluoro-5-trifluoromethylpyridin-2-yl)piperazin-1-yl)(5-methanesulfonyl-2-(2,2,2-trifluoro-1-methylethoxy)phenyl)methanone
unii-q8l6an59yy
(s)-(4-(3-fluoro-5-trifluoromethylpyridin-2-yl)piperazin-1-yl)(5-(methanesulfonyl)-2-(2,2,2-trifluoro-1-methylethoxy)phenyl)methanone
bitopertin [usan:inn]
D10186
bitopertin (jan/usan)
BCP9001046
HY-10809
CS-0939
S8219
SCHEMBL562490
[4-[3-fluoro-5-(trifluoromethyl)pyridin-2-yl]piperazin-1-yl]-[5-methylsulfonyl-2-[(2s)-1,1,1-trifluoropropan-2-yl]oxyphenyl]methanone
gtpl7546
rg1678
AKOS022185256
DTXSID80233556
[4-(3-fluoro-5-trifluoromethylpyridin-2-yl)piperazin-1-yl][5-methylsulfonyl-2-[((s)-2,2,2-trifluoro-1-methylethyl)oxy]phenyl]methanone
AC-33092
(4-(3-fluoro-5-(trifluoromethyl)pyridin-2-yl)piperazin-1-yl)(5-(methanesulfonyl)-2-(((2s)-1,1,1-trifluoropropan-2-yl)oxy)phenyl)methanone
bitopertin [who-dd]
methanone, (4-(3-fluoro-5-(trifluoromethyl)-2-pyridinyl)-1-piperazinyl)(5-(methylsulfonyl)-2-((1s)-2,2,2-trifluoro-1-methylethoxy)phenyl)-
bitopertin [inn]
disc-1459
bitopertin [usan]
bitopertin [jan]
methanone, [4-[3-fluoro-5-(trifluoromethyl)-2-pyridinyl]-1-piperazinyl][5-(methylsulfonyl)-2-[(1s)-2
mfcd18251496
(s)-(4-(3-fluoro-5-(trifluoromethyl)pyridin-2-yl)piperazin-1-yl)(5-(methylsulfonyl)-2-((1,1,1-trifluoropropan-2-yl)oxy)phenyl)methanone
NCGC00379029-01
DB12426
Q4918919
bitopertin (rg1678,ro-4917838)
AS-75194
1-[3-fluoro-5-(trifluoromethyl)pyridin-2-yl]-4-(5-methanesulfonyl-2-{[(2s)-1,1,1-trifluoropropan-2-yl]oxy}benzoyl)piperazine
HMS3886D08
CCG-269972
yuugyiuscynsqr-lbprgkrzsa-n

Protein Targets (10)

Potency Measurements

ProteinTaxonomyMeasurementAverage (mM)Bioassay(s)
cytochrome P450 family 3 subfamily A polypeptide 4Homo sapiens (human)Potency37.9083AID1645841
GVesicular stomatitis virusPotency6.7412AID1645842
cytochrome P450 2D6Homo sapiens (human)Potency21.3174AID1645840
Interferon betaHomo sapiens (human)Potency6.7412AID1645842
HLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)Potency6.7412AID1645842
Inositol hexakisphosphate kinase 1Homo sapiens (human)Potency6.7412AID1645842
cytochrome P450 2C9, partialHomo sapiens (human)Potency6.7412AID1645842

Inhibition Measurements

ProteinTaxonomyMeasurementAverage (mM)Bioassay(s)
Cytochrome P450 3A4Homo sapiens (human)Ki0.0470AID1356787
Sodium- and chloride-dependent glycine transporter 1Homo sapiens (human)Ki0.0470AID1356787

Other Measurements

ProteinTaxonomyMeasurementAverage (mM)Bioassay(s)
Sodium- and chloride-dependent glycine transporter 1Rattus norvegicus (Norway rat)Occ501.8000AID1663643

Bioassays (13)

Assay IDTitleYearJournalArticle
AID1347160Primary screen NINDS Rhodamine qHTS for Zika virus inhibitors2020Proceedings of the National Academy of Sciences of the United States of America, 12-08, Volume: 117, Issue:49
ISSN: 1091-6490		Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors.
AID1296008Cytotoxic Profiling of Annotated Libraries Using Quantitative High-Throughput Screening2020SLAS discovery : advancing life sciences R & D, 01, Volume: 25, Issue:1
ISSN: 2472-5560		Cytotoxic Profiling of Annotated and Diverse Chemical Libraries Using Quantitative High-Throughput Screening.
AID1346986P-glycoprotein substrates identified in KB-3-1 adenocarcinoma cell line, qHTS therapeutic library screen2019Molecular pharmacology, 11, Volume: 96, Issue:5
ISSN: 1521-0111		A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
AID1347159Primary screen GU Rhodamine qHTS for Zika virus inhibitors: Unlinked NS2B-NS3 protease assay2020Proceedings of the National Academy of Sciences of the United States of America, 12-08, Volume: 117, Issue:49
ISSN: 1091-6490		Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors.
AID1346987P-glycoprotein substrates identified in KB-8-5-11 adenocarcinoma cell line, qHTS therapeutic library screen2019Molecular pharmacology, 11, Volume: 96, Issue:5
ISSN: 1521-0111		A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
AID1751528Pro-social effect in po dosed BALB/c mouse assessed as sniffing index at 5 mg/kg, po measured after 60 mins by social interaction2021Journal of medicinal chemistry, 08-12, Volume: 64, Issue:15
ISSN: 1520-4804		Discovery of TAK-041: a Potent and Selective GPR139 Agonist Explored for the Treatment of Negative Symptoms Associated with Schizophrenia.
AID1356799Inhibition of GlyT1c (unknown origin) expressed in Xenopus laevis oocytes clamped at -60 mV assessed as reduction in 10 uM glycine-induced membrane currents at 300 nM pre-treated with glycine for 1 min followed by compound dosing for 3 mins by two-electro2018Journal of medicinal chemistry, 09-13, Volume: 61, Issue:17
ISSN: 1520-4804		Discovery of Novel Aminotetralines and Aminochromanes as Selective and Competitive Glycine Transporter 1 (GlyT1) Inhibitors.
AID1663643In vivo receptor occupancy at GlyT1 in Sprague-Dawley rat measured after 60 mins2020Bioorganic & medicinal chemistry letters, 07-15, Volume: 30, Issue:14
ISSN: 1464-3405		Azetidine-based selective glycine transporter-1 (GlyT1) inhibitors with memory enhancing properties.
AID1356787Displacement of [3H]N-Methyl-SSR504734 from human GlyT1c expressed in cell membranes incubated for 1 hr by liquid scintillation spectrometry2018Journal of medicinal chemistry, 09-13, Volume: 61, Issue:17
ISSN: 1520-4804		Discovery of Novel Aminotetralines and Aminochromanes as Selective and Competitive Glycine Transporter 1 (GlyT1) Inhibitors.
AID1356801Non-competitive inhibition of GlyT1c (unknown origin) expressed in Xenopus laevis oocytes clamped at -60 mV assessed as reduction in glycine-induced membrane currents at 300 nM pre-treated with glycine for 1 min followed by compound dosing for 3 mins by t2018Journal of medicinal chemistry, 09-13, Volume: 61, Issue:17
ISSN: 1520-4804		Discovery of Novel Aminotetralines and Aminochromanes as Selective and Competitive Glycine Transporter 1 (GlyT1) Inhibitors.
AID1356800Inhibition of GlyT1c (unknown origin) expressed in Xenopus laevis oocytes clamped at -60 mV assessed as reduction in 3000 uM glycine-induced membrane currents at 300 nM pre-treated with glycine for 1 min followed by compound dosing for 3 mins by two-elect2018Journal of medicinal chemistry, 09-13, Volume: 61, Issue:17
ISSN: 1520-4804		Discovery of Novel Aminotetralines and Aminochromanes as Selective and Competitive Glycine Transporter 1 (GlyT1) Inhibitors.
AID1347001Human GlyT2 (Glycine transporter subfamily)2010Journal of medicinal chemistry, Jun-24, Volume: 53, Issue:12
ISSN: 1520-4804		Selective GlyT1 inhibitors: discovery of [4-(3-fluoro-5-trifluoromethylpyridin-2-yl)piperazin-1-yl][5-methanesulfonyl-2-((S)-2,2,2-trifluoro-1-methylethoxy)phenyl]methanone (RG1678), a promising novel medicine to treat schizophrenia.
AID1346976Human GlyT1 (Glycine transporter subfamily)2010Journal of medicinal chemistry, Jun-24, Volume: 53, Issue:12
ISSN: 1520-4804		Selective GlyT1 inhibitors: discovery of [4-(3-fluoro-5-trifluoromethylpyridin-2-yl)piperazin-1-yl][5-methanesulfonyl-2-((S)-2,2,2-trifluoro-1-methylethoxy)phenyl]methanone (RG1678), a promising novel medicine to treat schizophrenia.

Research

Studies (43)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's0 (0.00)18.2507
2000's0 (0.00)29.6817
2010's35 (81.40)24.3611
2020's8 (18.60)2.80

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials14 (31.82%)5.53%
Reviews2 (4.55%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other28 (63.64%)84.16%
SubstanceStudiesClassesRolesFirst YearLast YearAverage AgeRelationship StrengthTrialspre-19901990's2000's2010'spost-2020
glycine
6
alpha-amino acid;
amino acid zwitterion;
proteinogenic amino acid;
serine family amino acid		EC 2.1.2.1 (glycine hydroxymethyltransferase) inhibitor;
fundamental metabolite;
hepatoprotective agent;
micronutrient;
neurotransmitter;
NMDA receptor agonist;
nutraceutical		201220227.0high000042
amphetamine
1
primary amine2012201212.0low000010
haloperidol
1
aromatic ketone;
hydroxypiperidine;
monochlorobenzenes;
organofluorine compound;
tertiary alcohol		antidyskinesia agent;
antiemetic;
dopaminergic antagonist;
first generation antipsychotic;
serotonergic antagonist		201720177.0low000010
ketoconazole
1
dichlorobenzene;
dioxolane;
ether;
imidazoles;
N-acylpiperazine;
N-arylpiperazine		201620168.0low100010
oxidopamine
1
benzenetriol;
catecholamine;
primary amino compound		drug metabolite;
human metabolite;
neurotoxin		202220222.0low000001
protoporphyrin ix
1
201620168.0low000010
risperidone
1
1,2-benzoxazoles;
heteroarylpiperidine;
organofluorine compound;
pyridopyrimidine		alpha-adrenergic antagonist;
dopaminergic antagonist;
EC 3.4.21.26 (prolyl oligopeptidase) inhibitor;
H1-receptor antagonist;
psychotropic drug;
second generation antipsychotic;
serotonergic antagonist		2014201410.0low000010
serine
1
L-alpha-amino acid;
proteinogenic amino acid;
serine family amino acid;
serine zwitterion;
serine		algal metabolite;
Escherichia coli metabolite;
human metabolite;
mouse metabolite;
Saccharomyces cerevisiae metabolite		201820186.0low100010
levodopa
1
amino acid zwitterion;
dopa;
L-tyrosine derivative;
non-proteinogenic L-alpha-amino acid		allelochemical;
antidyskinesia agent;
antiparkinson drug;
dopaminergic agent;
hapten;
human metabolite;
mouse metabolite;
neurotoxin;
plant growth retardant;
plant metabolite;
prodrug		202220222.0low000001
phencyclidine
1
benzenes;
piperidines		anaesthetic;
neurotoxin;
NMDA receptor antagonist;
psychotropic drug		2012201212.0low000010
erythromycin
1
cyclic ketone;
erythromycin		201620168.0low100010
n-methylaspartate
1
amino dicarboxylic acid;
D-alpha-amino acid;
D-aspartic acid derivative;
secondary amino compound		neurotransmitter agent201720177.0low000010
transferrin
1
201620168.0low000010
glutamic acid
1
glutamic acid;
glutamine family amino acid;
L-alpha-amino acid;
proteinogenic amino acid		Escherichia coli metabolite;
ferroptosis inducer;
micronutrient;
mouse metabolite;
neurotransmitter;
nutraceutical		2014201410.0low000010
moxifloxacin
1
aromatic ether;
cyclopropanes;
fluoroquinolone antibiotic;
pyrrolidinopiperidine;
quinolinemonocarboxylic acid;
quinolone antibiotic;
quinolone		antibacterial drug2012201212.0low100010
dizocilpine maleate
1
maleate salt;
tetracyclic antidepressant		anaesthetic;
anticonvulsant;
neuroprotective agent;
nicotinic antagonist;
NMDA receptor antagonist		202220222.0low000001
scopolamine hydrobromide
1
2014201410.0low000010
olanzapine
1
benzodiazepine;
N-arylpiperazine;
N-methylpiperazine		antiemetic;
dopaminergic antagonist;
histamine antagonist;
muscarinic antagonist;
second generation antipsychotic;
serotonergic antagonist;
serotonin uptake inhibitor		2014201410.0low100010
ConditionIndicatedStudiesFirst YearLast YearAverage AgeRelationship StrengthTrialspre-19901990's2000's2010'spost-2020
Anemia, Cooley's0
3
201820214.7low100021
Anemia, Hypochromic0
1
201620168.0low000010
Autosomal Dominant Juvenile Parkinson Disease0
1
202220222.0low000001
beta-Thalassemia1
3
201820214.7low100021
Cognition Disorders0
1
201820186.0low100010
Congenital Zika Syndrome0
1
202020204.0low000010
Dementia Praecox0
20
201020218.8high9001181
Depression, Involutional0
1
201720177.0low000010
Depressive Disorder, Major0
1
201720177.0low000010
Disease Models, Animal0
3
201620205.7low000030
Dyskinesia, Drug-Induced0
1
202220222.0low000001
Dyskinesia, Medication-Induced0
1
202220222.0low000001
Electrocardiogram QT Prolonged0
1
2012201212.0low100010
Extravascular Hemolysis0
1
201920195.0low000010
Hemolysis0
1
201920195.0low000010
Idiopathic Parkinson Disease0
1
202220222.0low000001
Iron Overload0
1
201920195.0low000010
Long QT Syndrome0
1
2012201212.0low100010
Parkinson Disease0
1
202220222.0low000001
Parkinsonian Disorders0
1
202220222.0low000001
Pregnancy0
1
201620168.0low000010
Schizophrenia1
20
201020218.8high9001181
Zika Virus Infection0
1
202020204.0low000010

Safety/Toxicity (4)

ArticleYear
Efficacy and safety of adjunctive bitopertin versus placebo in patients with suboptimally controlled symptoms of schizophrenia treated with antipsychotics: results from three phase 3, randomised, double-blind, parallel-group, placebo-controlled, multicent
The lancet. Psychiatry, , Volume: 3, Issue:12		2016
Preclinical Reproductive and Developmental Toxicity Profile of a Glycine Transporter Type 1 (Glyt1) Inhibitor.
Birth defects research. Part B, Developmental and reproductive toxicology, , Volume: 107, Issue:3		2016
A double-blind randomized study assessing safety and efficacy following one-year adjunctive treatment with bitopertin, a glycine reuptake inhibitor, in Japanese patients with schizophrenia.
BMC psychiatry, , Mar-15, Volume: 16		2016
Cardiovascular safety assessments in the cynomolgus monkey: Unmasking potential background arrhythmias in general toxicity studies.
Journal of pharmacological and toxicological methods, , Volume: 81

Long-term Use (1)

ArticleYear
Effect of glycine transporter 1 inhibition with bitopertin on parkinsonism and L-DOPA induced dyskinesia in the 6-OHDA-lesioned rat.
European journal of pharmacology, , Aug-15, Volume: 929		2022

Pharmacokinetics (4)

ArticleYear
Combining 'Bottom-Up' and 'Top-Down' Methods to Assess Ethnic Difference in Clearance: Bitopertin as an Example.
Clinical pharmacokinetics, , Volume: 55, Issue:7		2016
Effects of Cytochrome P450 3A4 Inhibitors-Ketoconazole and Erythromycin-on Bitopertin Pharmacokinetics and Comparison with Physiologically Based Modelling Predictions.
Clinical pharmacokinetics, , Volume: 55, Issue:2		2016
Physiologically based absorption modelling to predict the impact of drug properties on pharmacokinetics of bitopertin.
The AAPS journal, , Volume: 16, Issue:5		2014
Physiologically based pharmacokinetic modelling to predict single- and multiple-dose human pharmacokinetics of bitopertin.
Clinical pharmacokinetics, , Volume: 52, Issue:8		2013

Bioavailability (2)

ArticleYear
A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
Molecular pharmacology, , Volume: 96, Issue:5		2019
Physiologically based absorption modelling to predict the impact of drug properties on pharmacokinetics of bitopertin.
The AAPS journal, , Volume: 16, Issue:5		2014

Dosage (4)

ArticleYear
Preclinical Reproductive and Developmental Toxicity Profile of a Glycine Transporter Type 1 (Glyt1) Inhibitor.
Birth defects research. Part B, Developmental and reproductive toxicology, , Volume: 107, Issue:3		2016
Physiologically based absorption modelling to predict the impact of drug properties on pharmacokinetics of bitopertin.
The AAPS journal, , Volume: 16, Issue:5		2014
Physiologically based pharmacokinetic modelling to predict single- and multiple-dose human pharmacokinetics of bitopertin.
Clinical pharmacokinetics, , Volume: 52, Issue:8		2013
Evaluation of the effects of bitopertin (RG1678) on cardiac repolarization: a thorough corrected QT study in healthy male volunteers.
Clinical therapeutics, , Volume: 34, Issue:10		2012