BIFEPRUNOX

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

Structure Search

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)

HIDE SMILES / InChI

Molecular Formula	C24H23N3O2
Molecular Weight	385.4583
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/15707540 | https://globenewswire.com/news-release/2009/07/30/130354/0/en/Pipeline-update-following-an-interim-analysis-the-studies-with-bifeprunox-for-the-treatment-of-schizophrenia-is-discontinued.html

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.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Serotonin 1a (5-HT1a) receptor 172 Target ID: CHEMBL214 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15707540	Agonist 2678		8.0 null [pKi]
D(2) dopamine receptor 58 Target ID: P14416 Gene ID: 1813.0 Gene Symbol: DRD2 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/15707540	Partial Agonist 290		8.5 null [pKi]

Conditions

Condition	Modality	Highest Phase	Product
Schizophrenia 298 Sources: https://clinicaltrials.gov/ct2/show/NCT00366327	Primary	Phase III 656	Unknown Approved Use Unknown
Bipolar depression 9 Sources: https://clinicaltrials.gov/ct2/show/NCT00245973	Primary	Phase III 656	Unknown Approved Use Unknown
Parkinson's disease 226 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12625033	Primary	Phase I 428	Unknown Approved Use Unknown

AUC

Value	Dose	Co-administered	Analyte	Population
381.5 ng × h/mL REVIEW https://www.formularywatch.com/view/bifeprunox-partial-dopamine-receptor-agonist-treatment-schizophrenia	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 REVIEW https://www.formularywatch.com/view/bifeprunox-partial-dopamine-receptor-agonist-treatment-schizophrenia	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

F_unbound

Value	Dose	Co-administered	Analyte	Population
1% REVIEW https://www.formularywatch.com/view/bifeprunox-partial-dopamine-receptor-agonist-treatment-schizophrenia	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% REVIEW https://www.formularywatch.com/view/bifeprunox-partial-dopamine-receptor-agonist-treatment-schizophrenia	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

Sourcing

Vendor/Aggregator	ID	URL
Alfa Chemistry	ACM350992131	http://www.alfa-chemistry.com/search.aspx?q=ACM350992131
Angene	AGN-PC-0WH1IE	http://www.angenechemical.com/productshow/AGN-PC-0WH1IE.html
Axon MedChem	1508	https://www.axonmedchem.com/product/1508
BOC Sciences	350992-10-8	http://www.bocsci.com/description.asp?cas=350992-10-8
BOC Sciences	350992-13-1	http://www.bocsci.com/description.asp?cas=350992-13-1
Lab Network	LN01346299	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01346299
MolPort	MolPort-003-845-039	https://www.molport.com/shop/molecule-link/MolPort-003-845-039
MolPort	MolPort-005-943-082	https://www.molport.com/shop/molecule-link/MolPort-005-943-082
MuseChem	R005333	https://www.musechem.com/product/R005333.html
Otava	7070707030	https://search.otavachemicals.com/#!/search?query=7070707030&type=code
ShangHai Biochempartner	BCP02133	http://www.biochempartner.com/search_BCP02133
Toronto Research Chemicals	B383200	https://www.trc-canada.com/product-detail/?CatNum=B383200
Toronto Research Chemicals	D473080	https://www.trc-canada.com/product-detail/?CatNum=D473080
Wonderchem	WD05YDO	http://www.wonder-chem.com/search.html?text=WD05YDO
eMolecules	11313129	https://orderbb.emolecules.com/search/#?query=11313129
eMolecules	300123197	https://orderbb.emolecules.com/search/#?query=300123197
eMolecules	50891881	https://orderbb.emolecules.com/search/#?query=50891881
mcule	MCULE-8263015928	https://mcule.com/MCULE-8263015928/
mcule	MCULE-8477820759	https://mcule.com/MCULE-8477820759/

PubMed

Title	Date	PubMed
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	15996562
Molecule of the month. Bifeprunox mesilate.	2005 Oct	16391722
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	15987834
Novel antipsychotics activate recombinant human and native rat serotonin 5-HT1A receptors: affinity, efficacy and potential implications for treatment of schizophrenia.	2005 Sep	15707540
Aripiprazole: the evidence of its therapeutic impact in schizophrenia.	2006	22496680
Differential profile of antipsychotics at serotonin 5-HT1A and dopamine D2S receptors coupled to extracellular signal-regulated kinase.	2006 Mar 18	16497294
Partial agonist properties of the antipsychotics SSR181507, aripiprazole and bifeprunox at dopamine D2 receptors: G protein activation and prolactin release.	2006 Mar 27	16554049
Antipsychotic-like vs cataleptogenic actions in mice of novel antipsychotics having D2 antagonist and 5-HT1A agonist properties.	2006 Sep	16237379
Action of novel antipsychotics at human dopamine D3 receptors coupled to G protein and ERK1/2 activation.	2007 Aug	17588617
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	17532788
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	17393144
Pharmacological causes of hyperprolactinemia.	2007 Oct	18473017
Dopamine D2(High) receptors moderately elevated by bifeprunox and aripiprazole.	2008 Dec	18792990
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	18511034
Effects of antipsychotics and reference monoaminergic ligands on marble burying behavior in mice.	2008 Mar	18332679
Agonist and antagonist properties of antipsychotics at human dopamine D4.4 receptors: G-protein activation and K+ channel modulation in transfected cells.	2008 May	17897483
Apomorphine-induced emesis in dogs: differential sensitivity to established and novel dopamine D2/5-HT(1A) antipsychotic compounds.	2008 Nov 12	18773888
Differences among conventional, atypical and novel putative D(2)/5-HT(1A) antipsychotics on catalepsy-associated behaviour in cynomolgus monkeys.	2009 Nov 5	19464324
Tetrabenazine is neuroprotective in Huntington's disease mice.	2010 Apr 26	20420689
Development and application of an LC-MS/MS method for measuring the effect of (partial) agonists on cAMP accumulation in vitro.	2010 Apr 30	20122962
Dopamine D2-D3 receptor heteromers: pharmacological properties and therapeutic significance.	2010 Feb	19896900
The importance of 5-HT1A receptor agonism in antipsychotic drug action: rationale and perspectives.	2010 Jul	20571976
The effect of metformin on anthropometrics and insulin resistance in patients receiving atypical antipsychotic agents: a meta-analysis.	2010 Oct	20441727
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	20856922
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	21591752

Patents

Sample Use Guides

In Vivo Use Guide

Flex dose (20 or 30 mg)tablet, QD for 1 year

Route of Administration: Oral

In Vitro Use Guide

Unknown

Substance Class	Chemical Created by `admin` on `Fri Dec 15 16:38:33 GMT 2023` Edited by `admin` on `Fri Dec 15 16:38:33 GMT 2023`
Record UNII	AP69E83Z79
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

BIFEPRUNOX

Official Name

English

Bifeprunox [WHO-DD]

Common Name

English

bifeprunox [INN]

Common Name

English

7-[4-(Biphenyl-3-ylmethyl)piperazin-1-yl]benzoxazol-2(3H)-one

Systematic Name

English

BIFEPRUNOX [MI]

Common Name

English

BIFEPRUNOX [USAN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C29710