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Identification
NameBifeprunox
Accession NumberDB04888
TypeSmall Molecule
GroupsInvestigational
DescriptionBifeprunox 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 Identifiers
  • DU-127090
  • DU127090
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNIIAP69E83Z79
CAS number350992-10-8
WeightAverage: 385.4583
Monoisotopic: 385.179026995
Chemical FormulaC24H23N3O2
InChI KeyInChIKey=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
Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassBiphenyls and derivatives
Direct ParentBiphenyls and derivatives
Alternative Parents
Substituents
  • N-arylpiperazine
  • Biphenyl
  • Benzoxazolone
  • Benzoxazole
  • Dialkylarylamine
  • Phenylmethylamine
  • Benzylamine
  • Aralkylamine
  • N-alkylpiperazine
  • Piperazine
  • 1,4-diazinane
  • Heteroaromatic compound
  • Oxazole
  • Azole
  • Tertiary aliphatic amine
  • Tertiary amine
  • Oxacycle
  • Azacycle
  • Organoheterocyclic compound
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationBifeprunox is being evaluated for the treatment of schizophrenia, psychosis, and Parkinson's disease.
PharmacodynamicsBifeprunox 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 actionIn 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).
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
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 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental PropertiesNot 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 RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
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
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
3,4-MethylenedioxyamphetamineBifeprunox may decrease the stimulatory activities of 3,4-Methylenedioxyamphetamine.
3,4-MethylenedioxymethamphetamineBifeprunox may decrease the stimulatory activities of 3,4-Methylenedioxymethamphetamine.
AlmotriptanThe risk or severity of adverse effects can be increased when Almotriptan is combined with Bifeprunox.
AmisulprideThe risk or severity of adverse effects can be increased when Bifeprunox is combined with Amisulpride.
AmitriptylineThe risk or severity of adverse effects can be increased when Amitriptyline is combined with Bifeprunox.
AmoxapineThe risk or severity of adverse effects can be increased when Amoxapine is combined with Bifeprunox.
AmphetamineBifeprunox may decrease the stimulatory activities of Amphetamine.
BenzphetamineBifeprunox may decrease the stimulatory activities of Benzphetamine.
BromocriptineThe risk or severity of adverse effects can be increased when Bromocriptine is combined with Bifeprunox.
BuspironeThe risk or severity of adverse effects can be increased when Buspirone is combined with Bifeprunox.
CabergolineThe risk or severity of adverse effects can be increased when Cabergoline is combined with Bifeprunox.
ChlorphentermineBifeprunox may decrease the stimulatory activities of Chlorphentermine.
CitalopramThe risk or severity of adverse effects can be increased when Citalopram is combined with Bifeprunox.
ClomipramineThe risk or severity of adverse effects can be increased when Clomipramine is combined with Bifeprunox.
CyclobenzaprineThe risk or severity of adverse effects can be increased when Cyclobenzaprine is combined with Bifeprunox.
DesipramineThe risk or severity of adverse effects can be increased when Desipramine is combined with Bifeprunox.
DesvenlafaxineThe risk or severity of adverse effects can be increased when Desvenlafaxine is combined with Bifeprunox.
DextroamphetamineBifeprunox may decrease the stimulatory activities of Dextroamphetamine.
DextromethorphanThe risk or severity of adverse effects can be increased when Dextromethorphan is combined with Bifeprunox.
DihydroergotamineThe risk or severity of adverse effects can be increased when Dihydroergotamine is combined with Bifeprunox.
DoxepinThe risk or severity of adverse effects can be increased when Doxepin is combined with Bifeprunox.
DuloxetineThe risk or severity of adverse effects can be increased when Duloxetine is combined with Bifeprunox.
EletriptanThe risk or severity of adverse effects can be increased when Eletriptan is combined with Bifeprunox.
Ergoloid mesylateThe risk or severity of adverse effects can be increased when Ergoloid mesylate is combined with Bifeprunox.
ErgonovineThe risk or severity of adverse effects can be increased when Ergonovine is combined with Bifeprunox.
ErgotamineThe risk or severity of adverse effects can be increased when Ergotamine is combined with Bifeprunox.
EscitalopramThe risk or severity of adverse effects can be increased when Escitalopram is combined with Bifeprunox.
FentanylThe risk or severity of adverse effects can be increased when Fentanyl is combined with Bifeprunox.
FluoxetineThe risk or severity of adverse effects can be increased when Fluoxetine is combined with Bifeprunox.
FluvoxamineThe risk or severity of adverse effects can be increased when Fluvoxamine is combined with Bifeprunox.
FrovatriptanThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Bifeprunox.
Hydroxyamphetamine hydrobromideBifeprunox may decrease the stimulatory activities of Hydroxyamphetamine hydrobromide.
ImipramineThe risk or severity of adverse effects can be increased when Imipramine is combined with Bifeprunox.
IsocarboxazidThe risk or severity of adverse effects can be increased when Isocarboxazid is combined with Bifeprunox.
LevomilnacipranThe risk or severity of adverse effects can be increased when Levomilnacipran is combined with Bifeprunox.
LinezolidThe risk or severity of adverse effects can be increased when Linezolid is combined with Bifeprunox.
LisdexamfetamineBifeprunox may decrease the stimulatory activities of Lisdexamfetamine.
LithiumLithium may increase the neurotoxic activities of Bifeprunox.
LorcaserinThe risk or severity of adverse effects can be increased when Lorcaserin is combined with Bifeprunox.
MaprotilineThe risk or severity of adverse effects can be increased when Maprotiline is combined with Bifeprunox.
MephentermineBifeprunox may decrease the stimulatory activities of Mephentermine.
MequitazineBifeprunox may increase the arrhythmogenic activities of Mequitazine.
MethadoneThe risk or severity of adverse effects can be increased when Methadone is combined with Bifeprunox.
MethamphetamineBifeprunox may decrease the stimulatory activities of Methamphetamine.
MethylphenidateThe risk or severity of adverse effects can be increased when Bifeprunox is combined with Methylphenidate.
MetoclopramideThe risk or severity of adverse effects can be increased when Metoclopramide is combined with Bifeprunox.
MetyrosineThe risk or severity of adverse effects can be increased when Metyrosine is combined with Bifeprunox.
MilnacipranThe risk or severity of adverse effects can be increased when Milnacipran is combined with Bifeprunox.
MirtazapineThe risk or severity of adverse effects can be increased when Mirtazapine is combined with Bifeprunox.
MoclobemideThe risk or severity of adverse effects can be increased when Moclobemide is combined with Bifeprunox.
NaratriptanThe risk or severity of adverse effects can be increased when Naratriptan is combined with Bifeprunox.
NefazodoneThe risk or severity of adverse effects can be increased when Nefazodone is combined with Bifeprunox.
NortriptylineThe risk or severity of adverse effects can be increased when Nortriptyline is combined with Bifeprunox.
ParoxetineThe risk or severity of adverse effects can be increased when Paroxetine is combined with Bifeprunox.
PethidineThe risk or severity of adverse effects can be increased when Pethidine is combined with Bifeprunox.
PhenelzineThe risk or severity of adverse effects can be increased when Phenelzine is combined with Bifeprunox.
PhentermineBifeprunox may decrease the stimulatory activities of Phentermine.
ProcarbazineThe risk or severity of adverse effects can be increased when Procarbazine is combined with Bifeprunox.
PromethazineThe risk or severity of adverse effects can be increased when Promethazine is combined with Bifeprunox.
ProtriptylineThe risk or severity of adverse effects can be increased when Protriptyline is combined with Bifeprunox.
QuinagolideThe therapeutic efficacy of Quinagolide can be decreased when used in combination with Bifeprunox.
RasagilineThe risk or severity of adverse effects can be increased when Rasagiline is combined with Bifeprunox.
RizatriptanThe risk or severity of adverse effects can be increased when Rizatriptan is combined with Bifeprunox.
SelegilineThe risk or severity of adverse effects can be increased when Selegiline is combined with Bifeprunox.
SertralineThe risk or severity of adverse effects can be increased when Sertraline is combined with Bifeprunox.
SulpirideThe risk or severity of adverse effects can be increased when Bifeprunox is combined with Sulpiride.
SumatriptanThe risk or severity of adverse effects can be increased when Sumatriptan is combined with Bifeprunox.
TapentadolThe risk or severity of adverse effects can be increased when Tapentadol is combined with Bifeprunox.
Tedizolid PhosphateThe risk or severity of adverse effects can be increased when Tedizolid Phosphate is combined with Bifeprunox.
TetrabenazineThe risk or severity of adverse effects can be increased when Tetrabenazine is combined with Bifeprunox.
TramadolThe risk or severity of adverse effects can be increased when Tramadol is combined with Bifeprunox.
TranylcypromineThe risk or severity of adverse effects can be increased when Tranylcypromine is combined with Bifeprunox.
TrazodoneThe risk or severity of adverse effects can be increased when Trazodone is combined with Bifeprunox.
TrimipramineThe risk or severity of adverse effects can be increased when Trimipramine is combined with Bifeprunox.
VenlafaxineThe risk or severity of adverse effects can be increased when Venlafaxine is combined with Bifeprunox.
VilazodoneThe risk or severity of adverse effects can be increased when Vilazodone is combined with Bifeprunox.
VortioxetineThe risk or severity of adverse effects can be increased when Vortioxetine is combined with Bifeprunox.
ZolmitriptanThe risk or severity of adverse effects can be increased when Zolmitriptan is combined with Bifeprunox.
Food InteractionsNot Available

Targets

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
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 signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Beta-arrestin family members inhibit signaling via G pro...
Gene Name:
HTR1A
Uniprot ID:
P08908
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 ]
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Drug created on October 21, 2007 08:14 / Updated on August 17, 2016 12:24