Bifeprunox ( INN) (code name DU-127,090) is an atypical antipsychotic which, similarly to aripiprazole, combines minimal D₂ receptor

agonism Agonism (from Greek ἀγών '' agon'', "struggle") is a political and social theory that emphasizes the potentially positive aspects of certain forms of conflict. It accepts a permanent place for such conflict in the political sphere, but seeks ...

with

serotonin receptor 5-HT receptors, 5-hydroxytryptamine receptors, or serotonin receptors, are a group of G protein-coupled receptor and ligand-gated ion channels found in the central and peripheral nervous systems. They mediate both excitatory and inhibitory neur ...

agonism. It was under development for the treatment of schizophrenia but has since been abandoned.Pipeline update - following an interim analysis the studies with bifeprunox for the treatment of schizophrenia is discontinued
Lundbeck Press Release. 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 D₂

receptor antagonist A receptor antagonist is a type of receptor ligand or drug that blocks or dampens a biological response by binding to and blocking a receptor rather than activating it like an agonist. Antagonist drugs interfere in the natural operation of rece ...

s. 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 Lundbeck 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: Bifeprunox synth

The reaction of 3-bromobenzyl alcohol 5852-73-0with mesyl chloride gives 3-bromobenzyl methanesulfonate 2732-02-3(2). This is used to alkylate 7-piperazin-1-yl-3H-1,3-benzoxazol-2-one 05685-26-5(1) leading t
CID:28466745
(3). The additional benzene ring is added by Suzuki cross-coupling with phenylboronic acid, completing the synthesis of bifeprunox (4).

Synthesis

See also