Bifeprunox

Bifeprunox

Clinical data
ATC code	none
Identifiers
IUPAC name 7-[4-(biphenyl-3-ylmethyl)piperazin-1-yl]-1,3-benzoxazol-2(3H)-one
CAS Number	350992-10-8 N
PubChem CID	208951
ChemSpider	181044 Y
UNII	AP69E83Z79
ChEMBL	ChEMBL218166 Y
CompTox Dashboard (EPA)	DTXSID80188592
Chemical and physical data
Formula	C24H23N3O2
Molar mass	385.467 g·mol−1
3D model (JSmol)	Interactive image
SMILES O=C2Oc1c(cccc1N2)N5CCN(Cc4cccc(c3ccccc3)c4)CC5
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) Y Key:CYGODHVAJQTCBG-UHFFFAOYSA-N Y
NY (what is this?)  (verify)

Bifeprunox (INN) (code name DU-127,090) is an atypical antipsychotic which, similarly to aripiprazole, combines minimal D₂ receptor agonism with serotonin receptor agonism. It was under development for the treatment of schizophrenia but has since been abandoned.

Bifeprunox has a novel mechanism of action. Conventional antipsychotics are classed into typical and atypical. The typical antipsychotics, such as chlorpromazine and haloperidol, are potent D₂receptor antagonists. The atypical antipsychotics started with clozapine, these are classified as multireceptor interacting compounds, acting as an agonist towards 5-HT_1A and an antagonist towards D₂ receptors among other 5-HT and DA receptors. Bifeprunox and other novel atypical antipsychotics will instead of antagonizing D₂ receptors, will act as partial agonists, as well as partial agonists towards 5-HT_1A receptors.

In a multi-center, placebo-controlled study, 20 mg of bifeprunox was found to be significantly more effective than placebo at reducing symptoms of schizophrenia, with a low incidence of side effects.

An NDA for Bifeprunox was filed with the U.S. Food and Drug Administration in January 2007. The FDA rejected the application in August 2007. In June 2009, Solvay and Wyeth decided to cease development because "efficacy data did not support pursuing the existing development strategy of stabilisation of non-acute patients with schizophrenia."

Synthesis

A related structure is called Adoprazine. Improved Synthesis:

Synthesis Patent:

The reaction of 3-bromobenzyl alcohol [15852-73-0] with mesyl chloride gives 3-bromobenzyl methanesulfonate [82732-02-3] (2). This is used to alkylate 7-piperazin-1-yl-3H-1,3-benzoxazol-2-one [105685-26-5] (1) leading to CID:28466745 (3). The additional benzene ring is added by Suzuki cross-coupling with phenylboronic acid, completing the synthesis of bifeprunox (4).

See also

• Aripiprazole
• Pardoprunox