Details
| Stereochemistry | ACHIRAL |
| Molecular Formula | C24H23N3O2 |
| Molecular Weight | 385.4583 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
O=C1NC2=CC=CC(N3CCN(CC4=CC=CC(=C4)C5=CC=CC=C5)CC3)=C2O1
InChI
InChIKey=CYGODHVAJQTCBG-UHFFFAOYSA-N
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)
Bifeprunox, code name DU-127,090 is an atypical antipsychotic agent, which combines minimal D2 receptor agonism with 5-HT receptor agonism. Bifeprunox was in phase III of clinical trials for the treatment of schizophrenia, Bipolar Depression and in phase I for Parkinson's disease, but these studies were discontinued because efficacy data did not support pursuing the existing development strategy of stabilization of non-acute patients with schizophrenia.
Originator
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: CHEMBL214 |
8.0 null [pKi] | ||
Target ID: P14416 Gene ID: 1813.0 Gene Symbol: DRD2 Target Organism: Homo sapiens (Human) |
8.5 null [pKi] |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Primary | Unknown Approved UseUnknown |
|||
| Primary | Unknown Approved UseUnknown |
|||
| Primary | Unknown Approved UseUnknown |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
381.5 ng × h/mL |
20 mg 1 times / day multiple, oral dose: 20 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
BIFEPRUNOX plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
825.1 ng × h/mL |
40 mg 1 times / day multiple, oral dose: 40 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
BIFEPRUNOX plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
Funbound
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
1% |
20 mg 1 times / day multiple, oral dose: 20 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
BIFEPRUNOX plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
1% |
40 mg 1 times / day multiple, oral dose: 40 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
BIFEPRUNOX plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
PubMed
| Title | Date | PubMed |
|---|---|---|
| New 1-aryl-4-(biarylmethylene)piperazines as potential atypical antipsychotics sharing dopamine D(2)-receptor and serotonin 5-HT(1A)-receptor affinities. | 2001 Sep 3 |
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| DU-127090 Solvay/H Lundbeck. | 2003 Jan |
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| Novel antipsychotic agents with 5-HT(1A) agonist properties: role of 5-HT(1A) receptor activation in attenuation of catalepsy induction in rats. | 2005 Aug |
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| Molecule of the month. Bifeprunox mesilate. | 2005 Oct |
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| Contrasting contribution of 5-hydroxytryptamine 1A receptor activation to neurochemical profile of novel antipsychotics: frontocortical dopamine and hippocampal serotonin release in rat brain. | 2005 Oct |
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| Novel antipsychotics activate recombinant human and native rat serotonin 5-HT1A receptors: affinity, efficacy and potential implications for treatment of schizophrenia. | 2005 Sep |
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| Aripiprazole: the evidence of its therapeutic impact in schizophrenia. | 2006 |
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| Differential profile of antipsychotics at serotonin 5-HT1A and dopamine D2S receptors coupled to extracellular signal-regulated kinase. | 2006 Mar 18 |
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| Partial agonist properties of the antipsychotics SSR181507, aripiprazole and bifeprunox at dopamine D2 receptors: G protein activation and prolactin release. | 2006 Mar 27 |
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| In vivo occupancy of dopamine D2 receptors by antipsychotic drugs and novel compounds in the mouse striatum and olfactory tubercles. | 2006 Sep |
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| Antipsychotic-like vs cataleptogenic actions in mice of novel antipsychotics having D2 antagonist and 5-HT1A agonist properties. | 2006 Sep |
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| Drug-drug interactions associated with second-generation antipsychotics: considerations for clinicians and patients. | 2007 |
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| Discriminative stimulus properties of S32504, a novel D3/D2 receptor agonist and antiparkinson agent, in rats: attenuation by the antipsychotics, aripiprazole, bifeprunox, N-desmethylclozapine, and by selective antagonists at dopamine D2 but not D3 receptors. | 2007 Apr |
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| Action of novel antipsychotics at human dopamine D3 receptors coupled to G protein and ERK1/2 activation. | 2007 Aug |
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| Partial agonist actions of aripiprazole and the candidate antipsychotics S33592, bifeprunox, N-desmethylclozapine and preclamol at dopamine D(2L) receptors are modified by co-transfection of D(3) receptors: potential role of heterodimer formation. | 2007 Aug |
|
| Neuropharmacological profile of bifeprunox: merits and limitations in comparison with other third-generation antipsychotics. | 2007 Jul |
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| 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. | 2007 Jul |
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| Pharmacological profiles in rats of novel antipsychotics with combined dopamine D2/serotonin 5-HT1A activity: comparison with typical and atypical conventional antipsychotics. | 2007 Mar |
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| Differential agonist and inverse agonist profile of antipsychotics at D2L receptors coupled to GIRK potassium channels. | 2007 Mar |
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| Differences in agonist/antagonist properties at human dopamine D(2) receptors between aripiprazole, bifeprunox and SDZ 208-912. | 2007 Nov 28 |
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| Pharmacological causes of hyperprolactinemia. | 2007 Oct |
|
| Differential profile of typical, atypical and third generation antipsychotics at human 5-HT7a receptors coupled to adenylyl cyclase: detection of agonist and inverse agonist properties. | 2007 Oct |
|
| Upcoming agents for the treatment of schizophrenia: mechanism of action, efficacy and tolerability. | 2008 |
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| Bipolar depression: trial-based insights to guide patient care. | 2008 |
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| Partial agonist actions at dopamine D2L receptors are modified by co-transfection of D3 receptors: potential role of heterodimer formation. | 2008 |
|
| Dopamine D2(High) receptors moderately elevated by bifeprunox and aripiprazole. | 2008 Dec |
|
| Antipsychotics differ in their ability to internalise human dopamine D2S and human serotonin 5-HT1A receptors in HEK293 cells. | 2008 Feb 26 |
|
| Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. | 2008 Jan |
|
| Actions of novel agonists, antagonists and antipsychotic agents at recombinant rat 5-HT6 receptors: a comparative study of coupling to G alpha s. | 2008 Jul 7 |
|
| Effects of antipsychotics and reference monoaminergic ligands on marble burying behavior in mice. | 2008 Mar |
|
| Agonist and antagonist properties of antipsychotics at human dopamine D4.4 receptors: G-protein activation and K+ channel modulation in transfected cells. | 2008 May |
|
| Serotonergic approaches in the development of novel antipsychotics. | 2008 Nov |
|
| Characterization of aripiprazole partial agonist activity at human dopamine D3 receptors. | 2008 Nov 12 |
|
| Apomorphine-induced emesis in dogs: differential sensitivity to established and novel dopamine D2/5-HT(1A) antipsychotic compounds. | 2008 Nov 12 |
|
| Efficacy and safety of bifeprunox in patients with an acute exacerbation of schizophrenia: results from a randomized, double-blind, placebo-controlled, multicenter, dose-finding study. | 2008 Oct |
|
| The antipsychotics clozapine and olanzapine increase plasma glucose and corticosterone levels in rats: comparison with aripiprazole, ziprasidone, bifeprunox and F15063. | 2008 Sep 11 |
|
| Receptor reserve-dependent properties of antipsychotics at human dopamine D2 receptors. | 2009 Apr 1 |
|
| Bifeprunox and aripiprazole suppress in vivo VTA dopaminergic neuronal activity via D2 and not D3 dopamine autoreceptor activation. | 2009 Aug 21 |
|
| Effects of bifeprunox and aripiprazole on rat serotonin and dopamine neuronal activity and anxiolytic behaviour. | 2009 Mar |
|
| Differences among conventional, atypical and novel putative D(2)/5-HT(1A) antipsychotics on catalepsy-associated behaviour in cynomolgus monkeys. | 2009 Nov 5 |
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| Tetrabenazine is neuroprotective in Huntington's disease mice. | 2010 Apr 26 |
|
| Development and application of an LC-MS/MS method for measuring the effect of (partial) agonists on cAMP accumulation in vitro. | 2010 Apr 30 |
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| Dopamine D2-D3 receptor heteromers: pharmacological properties and therapeutic significance. | 2010 Feb |
|
| The importance of 5-HT1A receptor agonism in antipsychotic drug action: rationale and perspectives. | 2010 Jul |
|
| The effect of metformin on anthropometrics and insulin resistance in patients receiving atypical antipsychotic agents: a meta-analysis. | 2010 Oct |
|
| Not all partial dopamine D(2) receptor agonists are the same in treating schizophrenia. Exploring the effects of bifeprunox and aripiprazole using a computer model of a primate striatal dopaminergic synapse. | 2010 Sep 7 |
|
| Identification of N-propylnoraporphin-11-yl 5-(1,2-dithiolan-3-yl)pentanoate as a new anti-Parkinson's agent possessing a dopamine D2 and serotonin 5-HT1A dual-agonist profile. | 2011 Jul 14 |
Patents
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| Classification Tree | Code System | Code | ||
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NCI_THESAURUS |
C29710
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AP69E83Z79
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C65262
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8266
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100000089783
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CHEMBL218166
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SUB20312
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C509981
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BIFEPRUNOX
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m2484
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208951
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RR-138
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ACTIVE MOIETY
SALT/SOLVATE (PARENT)
