Penfluridol

Originator

Semap,Janssen-Le Brun ,W. Germany ,1975

Uses

antineoplastic

Uses

In terms of pharmacological action, penfluridol is similar to pimozide; however, it is significantly longer lasting, which is connected to the slow metabolism of the drug. Penfluridol is used as a supportive therapy in ambulatory settings for patients suffering from schizophrenia as well as patients with paranoid, psychotic, and neuroleptic conditions.

Uses

Penfluridol has been used as an antipsychotic agent:

• to study its antimetastatic effect on triple-negative breast cancer cells
• to study its effects on the growth of glioblastoma cell lines,
• to study its effects on the vascular endothelial growth factor (VEGF)-induced angiogenesis in human umbilical vein endothelial cells (HUVECs)

Definition

ChEBI: 1-[4,4-bis(4-fluorophenyl)butyl]-4-[4-chloro-3-(trifluoromethyl)phenyl]-4-piperidinol is a diarylmethane.

Manufacturing Process

A mixture of 24 parts of 4,4-bis(p-fluorophenyl)butyl chloride, 20.9 parts of 4(4-chloro-α,α,α-trifluoro-m-tolyl)-4-piperidinol, 13.8 parts of sodium carbonate, a few crystals of potassium iodide in 600 parts of 4-methyl-2pentanone is stirred and refluxed for 60 hours. The reaction mixture is cooled and 150 parts of water is added. The organic layer is separated, dried, filtered and evaporated. The oily residue is crystallized from diisopropylether, yielding 4-(4chloro-α,α,α-trifluoro-m-tolyl)-1-[4,4-bis(p-fiuorophenyl)butyl]-4piperidinol; melting point 106.5°C.

brand name

Semap (Ortho-McNeil).

Therapeutic Function

Antipsychotic

Biochem/physiol Actions

Penfluridol is studied in the treatment of schizophrenia, Tourette syndrome and acute psychosis. It also exhibits anticancer activity.

Safety Profile

Poison by ingestion and intravenous routes. Experimental teratogenic and reproductive effects. A neuroleptic agent. When heated to decomposition it emits very toxic fumes of Cl-, F-, and NOx.

Synthesis

Penfluridol, 4-(4-chloro-3-trifluoromethylphenyl)-1-[4,4-bis-(p-fluorophenyl) butyl]-4-piperidinol (6.6.12), is synthesized implementing a Grignard reaction between 1-carbomethoxypiperidin-4-one and 4-chloro-3-trifluoromethylphenylmagnesium bromide, giving 1-carbomethoxy-(4-chloro-3-trifluoromethylphenyl)-4-piperidinol (6.6.10). Upon alkaline hydrolysis of the carbomethoxy group, it turns into (4-chloro-3-trifluoromethylphenyl)-4-piperidinol (6.6.11), the alkylation of which with 1,1-bis(4-fluorophenyl)butyl bromide (6.6.3) gives penfluridol (6.6.12) [67¨C69].