BIFEPRUNOX MESYLATE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C24H23N3O2.CH4O3S
Molecular Weight	481.564
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CS(O)(=O)=O.O=C1NC2=CC=CC(N3CCN(CC4=CC=CC(=C4)C5=CC=CC=C5)CC3)=C2O1

InChI

InChIKey=ONWKHSGOYGLGPO-UHFFFAOYSA-N

InChI=1S/C24H23N3O2.CH4O3S/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;1-5(2,3)4/h1-11,16H,12-15,17H2,(H,25,28);1H3,(H,2,3,4)

HIDE SMILES / InChI

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
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	11527728
DU-127090 Solvay/H Lundbeck.	2003 Jan	12625033
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
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
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	17047933
Bipolar depression: trial-based insights to guide patient care.	2008	18689288
Antipsychotics differ in their ability to internalise human dopamine D2S and human serotonin 5-HT1A receptors in HEK293 cells.	2008 Feb 26	18190908
Serotonergic approaches in the development of novel antipsychotics.	2008 Nov	18621404
The antipsychotics clozapine and olanzapine increase plasma glucose and corticosterone levels in rats: comparison with aripiprazole, ziprasidone, bifeprunox and F15063.	2008 Sep 11	18640111
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

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

Name

Type

Language

BIFEPRUNOX MESYLATE

Official Name

English

7-(4-(BIPHENYL-3-YLMETHYL)PIPERAZIN-1-YL)BENZOXAZOL-2(3H)-ONE METHANESULPHONATE

Systematic Name

English

2(3H)-BENZOXAZOLONE, 7-(4-((1,1'-BIPHENYL)-3-YLMETHYL)-1-PIPERAZINYL)-, MONOMETHANESULFONATE

Systematic Name

English

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

Systematic Name

English

BIFEPRUNOX MESILATE

Common Name

English

BIFEPRUNOX METHANESULFONATE

Common Name

English

Bifeprunox mesylate [WHO-DD]

Common Name

English

DU127090

Code

English

BIFEPRUNOX MESYLATE [USAN]

Common Name

English

BIFEPRUNOX METHANESULFONATE [MI]

Common Name

English

DU-127090

Code

English

2(3H)-BENZOXAZOLONE, 7-(4-((1,1'-BIPHENYL)-3-YLMETHYL)-1-PIPERAZINYL)-, MONOMETHANESULPHONATE

Systematic Name

English

Classification Tree Code System Code

NCI_THESAURUS

C29710