Bifeprunox

Identification

Name
Bifeprunox
Accession Number
DB04888
Type
Small Molecule
Groups
Investigational
Description

Bifeprunox is a novel atypical antipsychotic agent which, along with SLV313, aripiprazole and SSR-181507 combines minimal D2 receptor agonism with 5-HT receptor agonism. [Wikipedia]

Structure
Thumb
Synonyms
  • Bifeprunox mesilate
  • Bifeprunoxum
External IDs
DU-127090 / DU127090
Categories
UNII
AP69E83Z79
CAS number
350992-10-8
Weight
Average: 385.4583
Monoisotopic: 385.179026995
Chemical Formula
C24H23N3O2
InChI Key
CYGODHVAJQTCBG-UHFFFAOYSA-N
InChI
InChI=1S/C24H23N3O2/c28-24-25-21-10-5-11-22(23(21)29-24)27-14-12-26(13-15-27)17-18-6-4-9-20(16-18)19-7-2-1-3-8-19/h1-11,16H,12-15,17H2,(H,25,28)
IUPAC Name
7-{4-[(3-phenylphenyl)methyl]piperazin-1-yl}-2,3-dihydro-1,3-benzoxazol-2-one
SMILES
O=C1NC2=C(O1)C(=CC=C2)N1CCN(CC2=CC(=CC=C2)C2=CC=CC=C2)CC1

Pharmacology

Indication

Bifeprunox is being evaluated for the treatment of schizophrenia, psychosis, and Parkinson's disease.

Structured Indications
Not Available
Pharmacodynamics

Bifeprunox is an atypical antipsychotic drug with mixed (agonist/antagonist) receptor activity with the neurotransmitters dopamine (D2/3/4) and serotonin. Bifeprunox differs from first-generation atypical antipsychotics in that it acts as a partial D2 agonist. This property is shared by aripiprazole, a drug already marketed in Europe and the US for treatment of schizophrenia. A placebo-controlled, dose-finding phase II trial in patients with schizophrenia showed that bifeprunox was both efficacious and well tolerated. Importantly, treatment with bifeprunox did not appear to cause some of the side effects seen with other atypicals agents in routine use, such as weight gain, hyperprolactinaemia and cardiotoxicity.

Mechanism of action

In contrast to D2 receptor antagonism, partial D2 agonism is believed to decrease dopamine activity in an overactive dopamine system while simultaneously increasing dopamine activity in regions of the brain where dopaminergic activity is too low. By blocking overstimulated receptors and stimulating underactive ones, partial D2 agonists act as dopamine stabilisers. In common with aripiprazole, bifeprunox also acts as a serotonin, 5-HT1A agonist. This property may contribute to efficacy against the negative symptoms of schizophrenia and reduce the likelihood of extrapyramidal symptoms (EPS).

TargetActionsOrganism
UD(2) dopamine receptorNot AvailableHuman
U5-hydroxytryptamine receptor 1ANot AvailableHuman
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
2,5-Dimethoxy-4-ethylamphetamineBifeprunox may decrease the stimulatory activities of 2,5-Dimethoxy-4-ethylamphetamine.Experimental, Illicit
3,4-MethylenedioxyamphetamineBifeprunox may decrease the stimulatory activities of 3,4-Methylenedioxyamphetamine.Experimental, Illicit
4-Bromo-2,5-dimethoxyamphetamineBifeprunox may decrease the stimulatory activities of 4-Bromo-2,5-dimethoxyamphetamine.Experimental, Illicit
AlmotriptanThe risk or severity of adverse effects can be increased when Almotriptan is combined with Bifeprunox.Approved, Investigational
AmisulprideThe risk or severity of adverse effects can be increased when Bifeprunox is combined with Amisulpride.Approved, Investigational
AmitriptylineThe risk or severity of adverse effects can be increased when Amitriptyline is combined with Bifeprunox.Approved
AmoxapineThe risk or severity of adverse effects can be increased when Amoxapine is combined with Bifeprunox.Approved
AmphetamineBifeprunox may decrease the stimulatory activities of Amphetamine.Approved, Illicit
BenzphetamineBifeprunox may decrease the stimulatory activities of Benzphetamine.Approved, Illicit
BromocriptineThe risk or severity of adverse effects can be increased when Bromocriptine is combined with Bifeprunox.Approved, Investigational
BuspironeThe risk or severity of adverse effects can be increased when Buspirone is combined with Bifeprunox.Approved, Investigational
CabergolineThe risk or severity of adverse effects can be increased when Cabergoline is combined with Bifeprunox.Approved
ChlorphentermineBifeprunox may decrease the stimulatory activities of Chlorphentermine.Illicit, Withdrawn
CitalopramThe risk or severity of adverse effects can be increased when Citalopram is combined with Bifeprunox.Approved
ClomipramineThe risk or severity of adverse effects can be increased when Clomipramine is combined with Bifeprunox.Approved, Vet Approved
CyclobenzaprineThe risk or severity of adverse effects can be increased when Cyclobenzaprine is combined with Bifeprunox.Approved
DesipramineThe risk or severity of adverse effects can be increased when Desipramine is combined with Bifeprunox.Approved
DesvenlafaxineThe risk or severity of adverse effects can be increased when Desvenlafaxine is combined with Bifeprunox.Approved
DextroamphetamineBifeprunox may decrease the stimulatory activities of Dextroamphetamine.Approved, Illicit
DextromethorphanThe risk or severity of adverse effects can be increased when Dextromethorphan is combined with Bifeprunox.Approved
DiethylpropionBifeprunox may decrease the stimulatory activities of Diethylpropion.Approved, Illicit
DihydroergotamineThe risk or severity of adverse effects can be increased when Dihydroergotamine is combined with Bifeprunox.Approved
DoxepinThe risk or severity of adverse effects can be increased when Doxepin is combined with Bifeprunox.Approved
DuloxetineThe risk or severity of adverse effects can be increased when Duloxetine is combined with Bifeprunox.Approved
EletriptanThe risk or severity of adverse effects can be increased when Eletriptan is combined with Bifeprunox.Approved, Investigational
Ergoloid mesylateThe risk or severity of adverse effects can be increased when Ergoloid mesylate is combined with Bifeprunox.Approved
ErgonovineThe risk or severity of adverse effects can be increased when Ergonovine is combined with Bifeprunox.Approved
ErgotamineThe risk or severity of adverse effects can be increased when Ergotamine is combined with Bifeprunox.Approved
EscitalopramThe risk or severity of adverse effects can be increased when Escitalopram is combined with Bifeprunox.Approved, Investigational
FentanylThe risk or severity of adverse effects can be increased when Fentanyl is combined with Bifeprunox.Approved, Illicit, Investigational, Vet Approved
FluoxetineThe risk or severity of adverse effects can be increased when Fluoxetine is combined with Bifeprunox.Approved, Vet Approved
FluvoxamineThe risk or severity of adverse effects can be increased when Fluvoxamine is combined with Bifeprunox.Approved, Investigational
FrovatriptanThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Bifeprunox.Approved, Investigational
GepefrineBifeprunox may decrease the stimulatory activities of Gepefrine.Experimental
HydroxyamphetamineBifeprunox may decrease the stimulatory activities of Hydroxyamphetamine.Approved
ImipramineThe risk or severity of adverse effects can be increased when Imipramine is combined with Bifeprunox.Approved
Iofetamine I-123Bifeprunox may decrease the stimulatory activities of Iofetamine I-123.Approved
IsocarboxazidThe risk or severity of adverse effects can be increased when Isocarboxazid is combined with Bifeprunox.Approved
LevomilnacipranThe risk or severity of adverse effects can be increased when Levomilnacipran is combined with Bifeprunox.Approved
LinezolidThe risk or severity of adverse effects can be increased when Linezolid is combined with Bifeprunox.Approved, Investigational
LisdexamfetamineBifeprunox may decrease the stimulatory activities of Lisdexamfetamine.Approved, Investigational
LithiumLithium may increase the neurotoxic activities of Bifeprunox.Approved
LorcaserinThe risk or severity of adverse effects can be increased when Lorcaserin is combined with Bifeprunox.Approved
MaprotilineThe risk or severity of adverse effects can be increased when Maprotiline is combined with Bifeprunox.Approved
MephedroneBifeprunox may decrease the stimulatory activities of Mephedrone.Investigational
MephentermineBifeprunox may decrease the stimulatory activities of Mephentermine.Approved
MequitazineBifeprunox may increase the arrhythmogenic activities of Mequitazine.Approved
MethadoneThe risk or severity of adverse effects can be increased when Methadone is combined with Bifeprunox.Approved
MethamphetamineBifeprunox may decrease the stimulatory activities of Methamphetamine.Approved, Illicit
MethoxyphenamineBifeprunox may decrease the stimulatory activities of Methoxyphenamine.Experimental
MethylphenidateThe risk or severity of adverse effects can be increased when Bifeprunox is combined with Methylphenidate.Approved, Investigational
MetoclopramideThe risk or severity of adverse effects can be increased when Metoclopramide is combined with Bifeprunox.Approved, Investigational
MetyrosineThe risk or severity of adverse effects can be increased when Metyrosine is combined with Bifeprunox.Approved
MidomafetamineBifeprunox may decrease the stimulatory activities of Midomafetamine.Experimental, Illicit, Investigational
MilnacipranThe risk or severity of adverse effects can be increased when Milnacipran is combined with Bifeprunox.Approved
MirtazapineThe risk or severity of adverse effects can be increased when Mirtazapine is combined with Bifeprunox.Approved
MMDABifeprunox may decrease the stimulatory activities of MMDA.Experimental, Illicit
MoclobemideThe risk or severity of adverse effects can be increased when Moclobemide is combined with Bifeprunox.Approved
NaratriptanThe risk or severity of adverse effects can be increased when Naratriptan is combined with Bifeprunox.Approved, Investigational
NefazodoneThe risk or severity of adverse effects can be increased when Nefazodone is combined with Bifeprunox.Approved, Withdrawn
NortriptylineThe risk or severity of adverse effects can be increased when Nortriptyline is combined with Bifeprunox.Approved
ParoxetineThe risk or severity of adverse effects can be increased when Paroxetine is combined with Bifeprunox.Approved, Investigational
PethidineThe risk or severity of adverse effects can be increased when Pethidine is combined with Bifeprunox.Approved
PhenelzineThe risk or severity of adverse effects can be increased when Phenelzine is combined with Bifeprunox.Approved
PhentermineBifeprunox may decrease the stimulatory activities of Phentermine.Approved, Illicit
ProcarbazineThe risk or severity of adverse effects can be increased when Procarbazine is combined with Bifeprunox.Approved
PromethazineThe risk or severity of adverse effects can be increased when Promethazine is combined with Bifeprunox.Approved
ProtriptylineThe risk or severity of adverse effects can be increased when Protriptyline is combined with Bifeprunox.Approved
PseudoephedrineBifeprunox may decrease the stimulatory activities of Pseudoephedrine.Approved
QuinagolideThe therapeutic efficacy of Quinagolide can be decreased when used in combination with Bifeprunox.Approved
RasagilineThe risk or severity of adverse effects can be increased when Rasagiline is combined with Bifeprunox.Approved
RitobegronBifeprunox may decrease the stimulatory activities of Ritobegron.Investigational
RizatriptanThe risk or severity of adverse effects can be increased when Rizatriptan is combined with Bifeprunox.Approved
SelegilineThe risk or severity of adverse effects can be increased when Selegiline is combined with Bifeprunox.Approved, Investigational, Vet Approved
SertralineThe risk or severity of adverse effects can be increased when Sertraline is combined with Bifeprunox.Approved
SulpirideThe risk or severity of adverse effects can be increased when Bifeprunox is combined with Sulpiride.Approved, Investigational
SumatriptanThe risk or severity of adverse effects can be increased when Sumatriptan is combined with Bifeprunox.Approved, Investigational
TapentadolThe risk or severity of adverse effects can be increased when Tapentadol is combined with Bifeprunox.Approved
Tedizolid PhosphateThe risk or severity of adverse effects can be increased when Tedizolid Phosphate is combined with Bifeprunox.Approved
TetrabenazineThe risk or severity of adverse effects can be increased when Tetrabenazine is combined with Bifeprunox.Approved
TramadolThe risk or severity of adverse effects can be increased when Tramadol is combined with Bifeprunox.Approved, Investigational
TranylcypromineThe risk or severity of adverse effects can be increased when Tranylcypromine is combined with Bifeprunox.Approved
TrazodoneThe risk or severity of adverse effects can be increased when Trazodone is combined with Bifeprunox.Approved, Investigational
TrimipramineThe risk or severity of adverse effects can be increased when Trimipramine is combined with Bifeprunox.Approved
VemurafenibThe risk or severity of QTc prolongation can be increased when Vemurafenib is combined with Bifeprunox.Approved
VenlafaxineThe risk or severity of adverse effects can be increased when Venlafaxine is combined with Bifeprunox.Approved
VilazodoneThe risk or severity of adverse effects can be increased when Vilazodone is combined with Bifeprunox.Approved
VortioxetineThe risk or severity of adverse effects can be increased when Vortioxetine is combined with Bifeprunox.Approved
ZolmitriptanThe risk or severity of adverse effects can be increased when Zolmitriptan is combined with Bifeprunox.Approved, Investigational
Food Interactions
Not Available

References

General References
  1. Newman-Tancredi A, Cussac D, Depoortere R: Neuropharmacological profile of bifeprunox: merits and limitations in comparison with other third-generation antipsychotics. Curr Opin Investig Drugs. 2007 Jul;8(7):539-54. [PubMed:17659474]
  2. Tadori Y, Kitagawa H, Forbes RA, McQuade RD, Stark A, Kikuchi T: Differences in agonist/antagonist properties at human dopamine D(2) receptors between aripiprazole, bifeprunox and SDZ 208-912. Eur J Pharmacol. 2007 Nov 28;574(2-3):103-11. Epub 2007 Aug 10. [PubMed:17692841]
External Links
PubChem Compound
208951
PubChem Substance
175426891
ChemSpider
181044
BindingDB
50241119
ChEMBL
CHEMBL218166
Wikipedia
Bifeprunox

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableHealthy Volunteers1
2CompletedTreatmentBipolar Disorder (BD) / Schizoaffective Disorders / Schizophrenic Disorders1
2CompletedTreatmentBipolar I Disorder1
2CompletedTreatmentSchizoaffective Disorders / Schizophrenic Disorders2
3CompletedTreatmentBipolar Disorder (BD)1
3CompletedTreatmentDepression Bipolar1
3CompletedTreatmentSchizophrenic Disorders5
3TerminatedTreatmentPsychosis and Behavioral Disturbances Associated With Dementia of the Alzheimer's Type1
3TerminatedTreatmentSchizophrenic Disorders6

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0197 mg/mLALOGPS
logP4.36ALOGPS
logP4.51ChemAxon
logS-4.3ALOGPS
pKa (Strongest Acidic)9.47ChemAxon
pKa (Strongest Basic)7.83ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area44.81 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity116.49 m3·mol-1ChemAxon
Polarizability43.09 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9887
Caco-2 permeable-0.5707
P-glycoprotein substrateSubstrate0.5278
P-glycoprotein inhibitor IInhibitor0.643
P-glycoprotein inhibitor IIInhibitor0.8377
Renal organic cation transporterInhibitor0.5
CYP450 2C9 substrateNon-substrate0.831
CYP450 2D6 substrateNon-substrate0.5751
CYP450 3A4 substrateSubstrate0.6164
CYP450 1A2 substrateInhibitor0.7388
CYP450 2C9 inhibitorInhibitor0.5321
CYP450 2D6 inhibitorNon-inhibitor0.6822
CYP450 2C19 inhibitorInhibitor0.7502
CYP450 3A4 inhibitorInhibitor0.5981
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.9391
Ames testNon AMES toxic0.6195
CarcinogenicityNon-carcinogens0.9333
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.5436 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Strong inhibitor0.6762
hERG inhibition (predictor II)Inhibitor0.5972
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as biphenyls and derivatives. These are organic compounds containing to benzene rings linked together by a C-C bond.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Biphenyls and derivatives
Direct Parent
Biphenyls and derivatives
Alternative Parents
N-arylpiperazines / Benzoxazolones / Benzylamines / Dialkylarylamines / Phenylmethylamines / N-alkylpiperazines / Aralkylamines / Heteroaromatic compounds / Oxazoles / Trialkylamines
show 6 more
Substituents
Biphenyl / N-arylpiperazine / Benzoxazolone / Benzoxazole / Benzylamine / Dialkylarylamine / Phenylmethylamine / Tertiary aliphatic/aromatic amine / Aralkylamine / N-alkylpiperazine
show 19 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Details
1. D(2) dopamine receptor
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Potassium channel regulator activity
Specific Function
Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase.
Gene Name
DRD2
Uniprot ID
P14416
Uniprot Name
D(2) dopamine receptor
Molecular Weight
50618.91 Da
References
  1. Auclair AL, Galinier A, Besnard J, Newman-Tancredi A, Depoortere R: Putative antipsychotics with pronounced agonism at serotonin 5-HT1A and partial agonist activity at dopamine D2 receptors disrupt basal PPI of the startle reflex in rats. Psychopharmacology (Berl). 2007 Jul;193(1):45-54. Epub 2007 Mar 29. [PubMed:17393144]
  2. Newman-Tancredi A, Cussac D, Depoortere R: Neuropharmacological profile of bifeprunox: merits and limitations in comparison with other third-generation antipsychotics. Curr Opin Investig Drugs. 2007 Jul;8(7):539-54. [PubMed:17659474]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Serotonin receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances. Ligand binding causes a conformation change that triggers...
Gene Name
HTR1A
Uniprot ID
P08908
Uniprot Name
5-hydroxytryptamine receptor 1A
Molecular Weight
46106.335 Da
References
  1. Bardin L, Kleven MS, Barret-Grevoz C, Depoortere R, Newman-Tancredi A: Antipsychotic-like vs cataleptogenic actions in mice of novel antipsychotics having D2 antagonist and 5-HT1A agonist properties. Neuropsychopharmacology. 2006 Sep;31(9):1869-79. Epub 2005 Oct 19. [PubMed:16237379]
  2. Auclair AL, Galinier A, Besnard J, Newman-Tancredi A, Depoortere R: Putative antipsychotics with pronounced agonism at serotonin 5-HT1A and partial agonist activity at dopamine D2 receptors disrupt basal PPI of the startle reflex in rats. Psychopharmacology (Berl). 2007 Jul;193(1):45-54. Epub 2007 Mar 29. [PubMed:17393144]
  3. Newman-Tancredi A, Cussac D, Depoortere R: Neuropharmacological profile of bifeprunox: merits and limitations in comparison with other third-generation antipsychotics. Curr Opin Investig Drugs. 2007 Jul;8(7):539-54. [PubMed:17659474]

Drug created on October 21, 2007 08:14 / Updated on December 01, 2017 15:34